Amide derivatives

ABSTRACT

A compound represented by the following general formula (1);                    
     wherein X represents R 1 (R 2 )(R 3 )C— where R 1  represents a C 3 -C 8  cycloalkyl group, an optionally substituted C 6 -C 14  aryl group, an optionally substituted heterocyclic residue, an optionally substituted C 6 -C 14  aryloxy group, or an optionally substituted C 7 -C 15  arylmethyl group; R 2  and R 3  independently represent hydrogen atom or a C 1 -C 5  alkyl group, or R 2  and R 3  may combine to represent a C 2 -C 7  alkylene group; or 
     X represents R 7 —A— wherein R 7  represents (i) a C1-C10 alkyl group which may optionally be substituted with an optionally substituted C6-C14 aryl group, an optionally substituted fluorenyl group or an optionally substituted heterocyclic group, (ii) an optionally substituted C6-C14 aryl group or (iii) an optionally substituted heterocyclic group, and A represents an oxygen atom or —N—R 8  where R 8  represents hydrogen atom or a C1-C5 alkyl group, 
     Y represents an oxygen atom or a sulfur atom, 
     R 4  and R 5  independently represent hydrogen atom or a C 1 -C 5  alkyl group; and R 6  represents hydrogen atom, a C 1 -C 5  alkyl group which may optionally be substituted with a hydroxyl group, a hydroxyl group or a C 1 -C 5  alkoxy group, 
     provided that the compounds wherein R 7  is a benzyl group, A and Y are an oxygen atom, R 4  and R 5  are hydrogen atom, and R 6  is a propyl group are excluded, or a salt thereof, or a solvate thereof or a hydrate thereof.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a continuation-in-part of U.S. applicationSer. No. 09/103,500, filed Jun. 24, 1998, now abandoned, and expresslyincorporates by reference herein the entire disclosure of U.S.application Ser. No. 09/103,500.

TECHNICAL FIELD

The present invention relates to novel amide derivatives having strongantibacterial activity against Helicobacter pylori.

BACKGROUND ART

Helicobacter pylori is a slightly aerobic gram-negative bacterium whichwas recently isolated from human gastric mucosa, and various publishedreports suggest its involvement in inflammation of alimentary tract,formation and recurrence of ulcer, and moreover, gastric cancer(Molecular Medicine, Vol. 31, pp. 1304-1374, 1994).

For the treatment of gastrointestinal ulcers, medicaments such as H₂blockers or proton pump inhibitors have been used so far. Since relationbetween Helicobacter pylori infection and gastric ulcer has been beingclarified as explained above, an antibacterial agent such as amoxicillinhas become practically used in combination, particularly from aviewpoint of prevention of recurrence. However, in most cases,ordinarily used antibacterial agents fail to achieve completeelimination of the bacteria. In addition, they may affect on intestinalbacterial flora due to their broad antibacterial spectra, and they oftencause adverse effects such as diarrhea. Therefore, it has been desiredto develop an antibacterial agent having potent antibacterial activityin alimentary tract that is specific against. Helicobacter pylori.

The compound represented by the general formula (I) defined herein belowwherein R⁷ is a benzyl group, and A and Y are an oxygen atom, and R⁴ andR⁵ are a hydrogen atom, and R⁶ is a propyl group, has been reported asintermediates of receptor models (Journal of American Chemical Society,Vol.115, pp. 3548, 1993). However, it has not been known that thiscompound has an antibacterial activity against Helicobacter pylori.

DISCLOSURE OF THE INVENTION

The inventors of the present invention conducted researches to provide anovel anti-Helicobacter pylori agent, and as a result, they found thatthe compounds represented by the following general formula haveexcellent antibacterial activity against Helicobacter pylori and canexhibit potent antibacterial activity in alimentary tract. The presentinvention was achieved on the basis of these findings.

The present invention thus provides amide derivatives represented by thefollowing general formula (I) and salts thereof, and solvates thereofand hydrates thereof:

wherein X represents R¹(R²)(R³)C— where R¹ represents a C₆-C₈ cycloalkylgroup, an optionally substituted C₆-C₁₄ aryl group, an optionallysubstituted heterocyclic residue wherein the heterocyclic residue is oneof furan ring, dihydrofuran ring, tetrahydrofuran ring, pyran ring,dihydropyran ring, tetrahydropyran ring, benzofuran ring,dihydrobenzofuran ring, isobenzofuran ring, chromene ring, chroman ring,isochroman ring, thiophene ring, benzothiophene ring, pyrrole ring,pyrroline ring, pyrrolidine ring, imidazole ring, imidazoline ring,imidazolidine ring, pyrazole ring, pyrazoline ring, pyrazolidine ring,triazole ring, tetrazole ring, pyridine ring, pyridineoxide ring,piperidine ring, pyrazine ring, piperazine ring, pyrimidine ring,pyridazine ring, indolizine ring, indole ring, indoline ring, isoindolering, isoindoline ring, indazole ring, benzimidazole ring, purine ring,quixolizine ring, quinoline ring, phthalazine ring, naphthylidine ring,quinoxaline ring, quinazoline ring, cinnoline ring, pteridine ring,oxazole ring, oxazolidine ring, isoxazole ring, isoxazolidine ring,thiazole ring, thiazylidine ring, isothiazole ring, isothiazolidinering, dioxane ring, dithian ring, morpholine ring, and thiomorpholinering, an optionally substituted C₆-C₁₄ aryloxy group, or an optionallysubstituted C₇-C₁₅ arylmethyl group; R² and R³ independently representhydrogen atom or a C₁-C₅ alkyl group, or R² and R³ may combine torepresent a C₂-C₇ aLkylene group; or

X represents R⁷—A— wherein R⁷ represents (i) a C1-C10 alkyl group whichmay optionally be substituted with an optionally substituted C6-C14 arylgroup, an optionally substituted fluorenyl group or an optionallysubstituted heterocyclic group, (ii) an optionally substituted C6-C14aryl group or (iii) an optionally substituted heterocyclic group, and Arepresents an oxygen atom or —N—R⁸ where R⁸ represents hydrogen atom ora C1-C5 alkyl group,

Y represents an oxygen atom or a sulfur atom,

R⁴ and R⁵ independently represent hydrogen atom or a C₁-C₅ alkyl group;and R⁶ represents hydrogen atom, a C₁-C₆ alkyl group which mayoptionally be substituted with a hydroxyl group, a hydroxyl group or aC₁-C₆ alkoxy group,

provided that the compounds wherein R⁷ is a benzyl group, A and Y are anoxygen atom, R⁴ and R⁵ are hydrogen atom, and R⁶ is a propyl group areexcluded, or a salt thereof, or a solvate thereof or a hydrate thereof.

According to another aspect of the present invention, the presentinvention provides medicaments, preferably for the treatment of gastricdiseases, e.g., gastritis, gastric ulcer, and gastric cancer, whichcomprise as an active ingredient a substance selected from the groupconsisting of the aforementioned amide derivatives and pharmaceuticallyacceptable salts thereof, and solvates thereof and hydrates thereof. Themedicaments are preferably provided as pharmaceutical compositionscomprising the aforementioned substance as an active ingredient togetherwith one or more pharmaceutically acceptable additives. Thesemedicaments can be used as anti-Helicobacter pylori agents fortherapeutic and/or preventive treatment of digestive diseases related toHelicobacter pylori infections for example, gastritis, gastric ulcer,gastric cancer, stomach malignant lymphoma, MALT lymphoma, duodenalulcer, duodenal carcinoma and the like.

According to further aspects of the present invention, there areprovided a method for treating digestive diseases related toHelicobacter pylori infection which comprises the step of administeringto a mammal including a human a therapeutically effective amount of asubstance selected from the group consisting of the aforementioned amidederivatives and pharmaceutically acceptable salts thereof, and solvatesthereof and hydrates thereof and a s of a substance selected from thegroup consisting of the aforementioned amide derivatives andpharmaceutically acceptable salts thereof, and solvates thereof andhydrates thereof for the manufacture of the above medicaments.

BEST MODE FOR CARRYING OUT THE INVENTION

In the general formula (I), examples of the C₆-C₈ cycloalkyl grouprepresented by R¹ include, for example, cyclopropyl group, cyclobutylgroup, cyclopentyl group, cyclohexyl group, cycloheptyl group, andcyclooctyl group. Examples of the C₆-C₁₄ aryl group include, forexample, aromatic hydrocarbon groups consisting of one ring or two toapproximately three condensed aromatic rings such as phenyl group,naphthyl group, and anthryl group.

As the residue of a heterocyclic compound, residues of heterocycliccompounds containing 1 to 4 heteroatoms selected from oxygen atom,sulfur atom, and nitrogen atom, and having 5 to 10 ring-membered atomsin total can be used. More specifically, examples of the residues ofheterocyclic compounds include, for example, furan ring, dihydrofuranring, tetrahydrofuran ring, pyran ring, dihydropyran ring,tetrahydropyran ring, benzofuran ring, dihydrobenzofuran ring,isobenzofuran ring, chromene ring, chroman ring, isochroman ring,thiophene ring, benzothiophene ring, pyrrole ring, pyrroline ring,pyrrolidine ring, imidazole ring, imidazoline ring, imidazohdine ring,pyrazole ring, pyrazoline ring, pyrazolidine ring, triazole ring,tetrazole ring, pyridine ring, pyridineoxide ring, piperidine ring,pyrazine ring, piperazine ring, pyrimidine ring, pyridazine ring,indolizine ring, indole ring, indoline ring, isoindole ring, isoindolinering, indazole ring, benzimidazole ring, purine ring, quinolie ring,quinoline ring, phthalazine ring, naphthylidine ring, quinoxaline ring,quinazoline ring, cinnoline ring, pteridine ring, oxazole ring,oxazolidine ring, isoxazole ring, isoxazolidine ring, thiazole ring,thiazylidine ring, isothiazole ring, isothiaolidine ring, dioxne ring,dithian ring, morpholine ring, and thiomorpholine ring. Examples of theC₆-C₁₄ aryloxy group include, for example, phenyloxy group, naphihyloxygroup, and anthryloxy group, and examples of the C₇-C₁₅ arylmethyl groupinclude, for example, benzyl group, naphthylmethyl group, andanthrylmethyl group.

The C₁-C₅ alkyl group independently represented by R² and R³ may beeither a straight or branched chain alkyl, and examples include, forexample, methyl group, ethyl group, propyl group, isopropyl group, butylgroup, isobutyl group, pentyl group, and isopentyl group. Examples ofthe C₂-C₇ alkylene group represented by R² combined with R³ include, forexample, ethylene group, trimethylene group, tetramethylene group,pentamethylene group, bexamethylene group, and heptamethylene group, andthese groups may have one or more branched chains.

As the C₁-C₅ alkyl group represented by R⁴ and R⁵, those explained forR² and R⁵ can be independently used. In the present invention, R⁴ and R⁵are preferably hydrogen atom.

As the C₁-C₅ alkyl group represented by R⁶, those explained for R² andR³ can be used, and these alkyl groups may be substituted with at leastone, preferably one hydroxy group. The C₁-C₅ alkoxy group represented byR⁶ may be a straight or branched chain group, and examples include, forexample, methoxy group, ethoxy group, propoxy group, isopropoxy group,butoxy group, isobutoxy group, tert-butoxy group, pentyloxy group, andisopentyloxy group. In the present invention, R⁶ is preferably an alkylgroup, more preferably a methyl group.

As the C₁-C₁₀ alkyl group represented by R⁷ in the general formula (I)above, those having a straight or branched chain can be used, andexamples include methyl group. ethyl group, propyl group, isopropylgroup, butyl group, isobutyl group, pentyl group, isopentyl group, hexylgroup, isohexyl group, heptyl group, octyl group, nonyl group, and decylgroup. These alkyl groups may optionally be substituted with a C₆-C₁₄aryl group, a fluorenyl group or a heterocyclic group. The C₆-C₁₄ arylgroup which can be a substituent on the alkyl group represented by R⁷includes, for example, a C₆-C₁₄ aryl group such as phenyl group, naphtylgroup or anthryl group. The heterocyclic group which can be asubstituent on the alkyl group represented by R⁷ includes, for example,those described for R¹.

As the C₆-C₁₄ aryl group and the heterocyclic group represented by R⁷,those described for the substituent on the C₁-C₁₀ alkyl group can beused.

R⁷ is preferably a C₁-C₁₀ alkyl group which may optionally besubstituted with an optionally substituted C₆-C₁₄ aryl group or anoptionally substituted heterocyclic group, more preferably a C₁-C₅ alkylgroup which may optionally be substituted with an optionally substitutedC₆-C₁₄ aryl group or an optionally substituted heterocyclic group, stillmore preferably a methyl group which may optionally be substituted withan optionally substituted C6-C14 aryl group or an optionally substitutedheterocyclic group. In the present invention, R⁷ is particularlypreferably a methyl group which is subsituted with an optionallysubstituted C₆-C₁₄ aryl group or a methyl group which is substitutedwith an optionally substituted heterocyclic group.

A represents an oxygen atom or —N—R⁸ wherein R⁸ represents hydrogen atomor a C₁-C₅ alkyl group. The C₁-C₅ alkyl group represented by R⁸ includesmethyl group, ethyl group, propyl group, isopropyl group, butyl group,isobutyl group, pentyl group, and isopentyl group. A is preferably anoxygen atom or —N—H.

Y represents an oxygen atom or a sulfur atom. Y is preferably an oxygenatom.

The aforementioned aryl group, residue of a heterocyclic compound,aryloxy group, and arylmethyl group may have one or more subituents atarbitrary positions on their rings Examples of substituents include, forexample, a halogen atom such as fluorine atom, chlorine atom, andbromine atom; a C₁-C₅ alkyl group such as methyl group, ethyl group,propyl group, isopropyl group, butyl group, isobutyl group, sec-butylgroup, tertbutyl group, pentyl group, isopentyl group, neopentyl group,and tertentyl group; a C₇-C₁₅ aralkyl group such as benzyl group,phenylethyl group, and naphtbylmethyl group; trifluoromethyl group; aC₁-C₅ alkoxy group such as methoxy group, ethoxy group, propoxy group,isopropoxy group, butoxy group, isobutoxy group, tert-butoxy group,pentyloxy group, and isopentyloxy group; a C₇-C₁₅ aralkyloxy group suchas benzyloxy group, phenylethyloxy group, and naphthylmethyloxy group; aC₁-C₅ alkylenedioxy group such as methylenedioxy group, ethylenedioxygroup, and propylenedioxy group; hydroxy group; nitro group; a C₂-C₆alkylcarbonyloxy group such as acetoxy group, propionyloxy group,butyryloxy group, and valeryloxy group; carboxyl group; a C₂-C₆alkoxycarbonyl group such as methoxycarbonyl group, ethoxycarbonylgroup, propoxycarbonyl group, isopropoxycarbonyl group, butoxycarbonylgroup, isobutoxycarbonyl group, tert-butoxycarbonyl group, andpentyloxycarbonyl group; a C₇-C₁₅ aralkyloxycarbonyl group such asbenzyloxycarbonyl group, phenylethyloxycarbonyl group, andnaphthylmethyloxycarbonyl group; oxo group; a C₂-C₆ alkylcarbonyt groupsuch as acetyl group, propionyl group, butyryl group, and valeryl group;mino group; a C₁-C₅ monoalkylamino group such as methylamino group,ethylamino group, propylamino group, isopropylamino group, butylaxninogroup, isobutylamino group, tertbutylamino group, pentylamio group, andisopentylamino group; a C₂-C₁₀ dialkylahino group such as dimethylaminogroup, etbylmethylamino group, diethylamino group, methylpropylaminogroup, and disopropylnino group; a C₂-C₆ alkylcarbonylamino group suchas acetylamino group, propionylamino group, isopropionylamino group,butyrylamino group, and valerylamino group; a C₂-C₆ alkylcarbonylaminogroup such as methoxycarbonylamino group, ethoxycarbonylamino group,propoxycarbonylamino group, isopropoxycarbonylamino group,butoxycarbonylamino group, isobutoxycarbonylamino group,tert-butoxycarbony no group, and pentyloxycarbonylamino group; a C₇-C₁₅aralkyloxycarbonylamino group such as benzyloxycarbonylamino group,phenylethyloxycarbonylamino group, and naphthylmethyloxycarbonylaminogroup; carbamoyl group; a C₂-C₆ alkylrarbamoyl group such asmethylcarbamoyl group, etbylcarbamoyl group, propylcarbamoyl group,butylcarbamoyl group, tert-butylcarbamoyl group, and pentylcarbamoylgroup; a C₆-C₁₂ aryl group such as phenyl group, and naphthyl group andthe like.

Among the compounds of the present invention represented by the aboveformula (I) wherein X is R¹(R²)(R³)C—, preferred compounds include thosewherein R¹ is a C₆-C₁₄ aryl group which may optionally be substituted, aresidue of a heterocyclic compound which may optionally be substituted,a C₆-C₁₄ aryloxy group which may optionally be subsituted, or a C₇-C₁₅arylmethyl group which may optionally be substituted, R², R³, R⁴ and R⁵are hydrogen atoms R⁶ is a C₁-C₅ alkyl group, and Y is an oxygen atom.More preferred compounds include those wherein R¹ is a C₆-C₁₄ aryl groupwhich may optionally be substituted, a residue of a heterocycliccompound which may optionally be substituted, a C₆-C₁₄ aryloxy groupwhich may optionally be substituted, or a C₇-C₁₅ arylmethyl group whichmay optionally be substituted, R², R³, R⁴ and R⁵ are hydrogen atoms, R⁶is methyl group, and Y is an oxygen atom.

Examples of particularly preferred compounds include:

N-(3-methylcarbamoylphenyl)-3-chlorophenylacetamide;

N-(3-methylcarbamoylphenyl)-4-chlorophenylacetamide;

N-(3-methylcarbamoylphenyl)-3-bromophenylacetamide;

N-(3-methylcarbamoylphenyl)-4-bromophenylacetamide;

N-(3-methylcarbamoylphenyl)-3-methylphenylacetamide;

N-(3-methylcarbamoylphenyl)-4-methylphenylacetamide;

N-(3-methylcarbamoylphenyl)-3-methoxyphenylacetamide;

N-(3-methylcarbamoylphenyl)-4-methoxyphenylacetamide;

N-(3-methylcarbamoylphenyl)-3,4,5-trimethoxyphenylacetamide;

N-(3-methylcarbamoylphenyl)-3-benzyloxyphenylacetamide;

N-(3-methylcarbamoylphenyl)-1-naphthylactamide;

N-(3-methylcarbamoylphenyl)-2-naphthylacetamide;

N-(3-methy)carbamoylphenyl)-3-indolylacetamide;

N-(3-methylcarbamoylphenyl)-3-benzothienylacetamide;

N-(3-methylcarbamoylphenyl)-4-benzothienylacetamide;

N-(3-methylcarbamoylphenyl)-3,4-methylenedioxyphenylacetamide;

N-(3-methylcarbamoylphenyl)-2-chilorophenoxyacetanude;

N-(3-methylcarbamoylphenyl)-2,3-dichlorophenoxyacetamide;

N-(3-mcthylcarbaroylpbenyl)-1-naphthyloxyacetamitde;

N-(3-methylcarbamoy)phenyl)-2-naphthyloxyacetamide; and

N-(3-methylcarbamoylphenyl)-3-(2-methoxyphenyl)propionamide.

Among the compounds of the above formula (I) wherein X is R⁷—A—,preferred. compounds include those wherein R⁴ and R⁵ are hydrogen atom,A is an oxygen atom or —N—H and Y is an oxygen atom, or apharmaceutically acceptable salt thereof, or a solvate thereof or ahydrate thereof. More preferred compounds include those wherein R⁷ is amethyl group which is substituted with an optionally substituted C₆-C₁₄aryl group or heterocyclic group, R⁴ and R⁵ are hydrogen atom, R⁶ is amethyl group, A is an oxygen atom or —N—H and Y is an oxygen atom, or apharmaceutically acceptable salt thereof, or a solvate thereof or ahydrate thereof.

Particularly preferred compounds include a compound selected from thegroup consisting of:

N′-methyl-3-(2-chlorobenzyloxycarbonylamino)benzamide;

N′-methyl-3-(4-chlorobenzyloxycarbonylamino)benzamide;

N′-methyl-3-(2,3-dichlorobenzyloxycarbonylamino)benzamide;

N′-methyl-3-(2,6-dichlorobenzyloxycarbonylamino)benzamide;

N′-methyl-3-(2-bromobenzyloxycarbonylamino)benzamide;

N′-methyl-3-(2-methylbenzyloxycarbonylamino)benzamide;

N′-methyl-3-(3-methylbenzyloxycarbonylamino)benzamide;

N′-methyl-3-(4-methylbenzyloxycarbonylamino)benzamide;

N′-methyl-3-(1-naphthylmethoxycarbonylamino)benzamide; and

N′-methyl-3-(2-naphthylbethoxycarbonylamino)benzamide;

or a pharmaceutically acceptable salt thereof, or a solvate thereof or ahydrate thereof.

The amide derivatives of the present invention represented by the abovegeneral formula (I) can form a salt. Where one or more acidic groupsexist, examples of salts include, for example, metal salts such aslithium salt, sodium salt, potassium salt, magnesium salt, and calciumsalt and ammonium salts such as inorganic ammonium salt, methylammoniumsalt, dimethylammonium salt, trimethylanmionium salt, anddicyclohexylammxuonium salt. Where one or more basic groups exist,examples of salts include, for example, mineral acid salts such ashydrochloride, hydrobromide, sulfate, nitrate, and phosphate, andorganic acid salts such as methanesulfonate, benzenesulfonate,p-toluenesulfonate, acetate, propionate, tartrate, fumarate, maleate,malate, oxalate, succinate, citrate, benzoate, mandelate, cinnamate, andlactate. Pharmaceutically acceptable salts are preferred as the activeingredient of the medicaments of the present invention,. The amidederivatives of the present invention represented by the above generalformula (I) and salts thereof may also exist as solvates or hydrates.Any substances in the form of salts, solvates, or hydrates as well ascompounds in free forms fall within the scope of the present invention.

As to the stereochemistry of asymmetric carbon atoms present in theamide derivatives of the present invention represented by the generalformula (I), the atoms can independently be in (S), (R), or (RS)configuration. Isomers in pure forms based on one or more asymmetriccarbon atoms, e.g., enantiomers and diastereoisomers, any mixturesofsuch isomers, racemates and the like fall within the scope of thepresent invention.

Examples of specific examples of the amide derivatives of the presentinvention represented by the above general formula (I) wherein X isR¹(R²)(R³)C—, and Y is an oxygen atom, include those listed in Table 1.

TABLE 1 Compd. No. R¹ R² R³ R⁴ R⁵ R⁶ 1

H H H H CH₃ 2

H H H H CH₃ 3

H H H H CH₃ 4

H H H H CH₃ 5

H H H H CH₃ 6

H H H H CH₃ 7

H H H H CH₃ 8

CH₃ H H H CH₃ 9

CH₃ CH₃ H H CH₃ 10

CH₃ CH₃ CH₃ H CH₃ 11

—(CH₂)₄— H H CH₃ 12

—(CH₂)₅— H H CH₃ 13

H H H H CH₃ 14

H H H H CH₃ 15

H H H H CH₃ 16

H H H H CH₃ 17

H H H H CH₃ 18

H H H H CH₃ 19

H H H H CH₃ 20

H H H H H 21

H H CH₃ H CH₃ 22

H H H H CH₃ 23

H H H CH₃ CH₃ 24

H H H H CH₂CH₃ 25

H H H H CH₂CH₂CH₃ 26

H H H H (CH₂)₃CH₃ 27

H H H H (CH₂)₄CH₃ 28

H H H H CH₂CH₂OH 29

H H H H OH 30

H H H H OCH₃ 31

H H H H OCH₂CH₃ 32

H H H CH₂CH₃ CH₂CH₃ 33

H H H H CH₃ 34

H H H H CH₃ 35

H H H H CH₃ 36

H H H H CH₃ 37

H H H H CH₃ 38

H H H H CH₃ 39

H H H H CH₃ 40

H H H H CH₃ 41

H H H H CH₃ 42

H H H H CH₃ 43

H H H H CH₃ 44

H H H H CH₃ 45

H H H H CH₃ 46

H H H H CH₃ 47

H H H H CH₃ 48

H H H H CH₃ 49

H H H H CH₃ 50

H H H H CH₃ 51

H H H H CH₃ 52

H H H H CH₃ 53

H H H H CH₃ 54

H H H H CH₃ 55

H H H H CH₃ 56

H H H H CH₃ 57

H H H H CH₃ 58

H H H H CH₃ 59

H H H H CH₃ 60

H H H H CH₃ 61

H H H H CH₃ 62

H H H H CH₃ 63

H H H H CH₃ 64

H H H H CH₃ 65

H H H H CH₃ 66

H H H H CH₃ 67

H H H H CH₃ 68

H H H H CH₃ 69

H H H H CH₃ 70

H H H H CH₃ 71

H H H H H 72

H H H H CH₃ 73

H H H H CH₃ 74

H H H H CH₃ 75

H H H H CH₃ 76

H H H H CH₃ 77

H H H H CH₃ 78

H H H H CH₃ 79

H H H H CH₃ 80

H H H H CH₃ 81

H H H H CH₃ 82

H H H H CH₃ 83

H H H H CH₃ 84

H H H H CH₃ 85

H H H H CH₃ 86

H H H H CH₃ 87

H H H H CH₃ 88

H H H H CH₃ 89

H H H H CH₃ 90

H H H H CH₃ 91

H H H H CH₃ 92

H H H H CH₃ 93

H H H H CH₃ 94

H H H H CH₃ 95

H H H H CH₃ 96

H H H H CH₃ 97

H H H H CH₃ 98

H H H H CH₃ 99

H H H H CH₃ 100

H H H H CH₃ 101

H H H H CH₃ 102

H H H H CH₃ 103

H H H H CH₃ 104

H H H H CH₃ 105

H H H H CH₃ 106

H H H H CH₃ 107

H H H H CH₃ 108

H H H H CH₃ 109

H H H H CH₃ 110

H H H H CH₃ 111

H H H H CH₃ 112

H H H H CH₃ 113

H H H H CH₃ 114

H H H H CH₃ 115

H H H H CH₃ 116

H H H H CH₃ 117

H H H H CH₃ 118

H H H H CH₃ 119

H H H H CH₃ 120

H H H H CH₃ 121

H H H H CH₃ 122

H H H H CH₃ 123

H H H H CH₃ 124

H H H H CH₃ 125

H H H H CH₃ 126

H H H H CH₃ 127

H H H H CH₃ 128

H H H H CH₃ 129

H H H H CH₃ 130

H H H H CH₃ 131

H H H H CH₃ 132

H H H H CH₃ 133

H H H H CH₃ 134

H H H H CH₃ 135

H H H H CH₃ 136

H H H H CH₃ 137

H H H H CH₃ 138

H H H H CH₃ 139

H H H H CH₃ 140

H H H H CH₃ 141

H H H H CH₃ 142

H H H H CH₃ 143

H H H H CH₃ 144

H H H H CH₃ 145

H H H H CH₃ 146

H H H H CH₃ 147

H H H H CH₃ 148

H H H H CH₃ 149

H H H H CH₃ 150

H H H H CH₃ 151

H H H H CH₃ 152

H H H H CH₃ 153

H H H H CH₃ 154

H H H H CH₃ 155

H H H H CH₃ 156

CH₃ H H H CH₃ 157

CH₃ CH₃ H H CH₃ 158

H H H H CH₃ 159

H H H H CH₃ 160

H H H H CH₃ 161

H H H H CH₃ 162

H H H H CH₃ 163

H H H H CH₃ 164

H H H H CH₃ 165

H H H H CH₃ 166

H H H H CH₃ 167

H H H H CH₃ 168

H H H H CH₃ 169

H H H H CH₃ 170

H H H H CH₃ 171

H H H H CH₃ 172

H H H H CH₃ 173

H H H H CH₃ 174

H H H H CH₃ 175

H H H H CH₃ 176

H H H H CH₃ 177

H H H H CH₃ 178

H H H H CH₃ 179

H H H H CH₃ 180

H H H H CH₃ 181

H H H H CH₃ 182

H H H H CH₃ 183

H H H H CH₃ 184

H H H H CH₃ 185

H H H H CH₃ 186

H H H H CH₃ 187

H H H H CH₃ 188

H H H H CH₃ 189

H H H H CH₃ 190

H H H H CH₃ 191

H H H H CH₃ 192

H H H H CH₃ 193

H H H H CH₃ 194

H H H H CH₃ 195

H H H H CH₃ 196

H H H H CH₃ 197

H H H H CH₃ 198

H H H H CH₃ 199

H H H H CH₃ 200

H H H H CH₃ 201

H H H H CH₃ 202

H H H H CH₃ 203

H H H H CH₃ 204

H H H H CH₃ 205

H H H H CH₃ 206

H H H H CH₃ 207

H H H H CH₃ 208

H H H H CH₃ 209

H H H H CH₃ 210

H H H H CH₃ 211

H H H H CH₃ 212

H H H H CH₃ 213

H H H H CH₃ 214

H H H H CH₃ 215

H H H H CH₃ 216

H H H H CH₃ 217

H H H H CH₃ 218

H H H H CH₃ 219

H H H H CH₃ 220

H H H H CH₃ 221

H H H H CH₃ 222

H H H H CH₃ 223

H H H H CH₃ 224

H H H H CH₃ 225

H H H H CH₃ 226

H H H H CH₃ 227

H H H H CH₃ 228

H H H H CH₃ 229

H H H H CH₃ 230

H H H H CH₃ 231

H H H H CH₃ 232

H H H H CH₃ 233

H H H H CH₃ 234

H H H H CH₃ 235

H H H H CH₃ 236

H H H H CH₃ 237

H H H H CH₃ 238

H H H H CH₃ 239

H H H H CH₃ 240

H H H H CH₃ 241

H H H H CH₃ 242

H H H H CH₃ 243

H H H H CH₃ 244

H H H H CH₃ 245

H H H H CH₃ 246

H H H H CH₃ 247

H H H H CH₃ 248

H H H H CH₃ 249

H H H H CH₃ 250

H H H H CH₃ 251

H H H H CH₃ 252

H H H H CH₃

Examples of specific examples of the amide derivatives of the presentinvention represented by the above general formula (I) wherein X isR⁷—A—, include those listed in Table 2.

TABLE 2 Compd. No. R⁷ A Y R⁴ R⁵ R⁶ 1 CH₃ O O H H CH₃ 2 NH O 3 4 5 6

O O NH NH O S O S H H CH₃ 7 8

O NH O O H H H 9 10

O NH O O H CH₃ CH₃ 11 12

O NH O O H H CH₂CH₃ 13 14

O NH O O H H CH₂CH₂CH₃ 15 16

O NH O O CH₃ H CH₃ 17 18

O NH O O H H CH₃ 19 20

O NH O O H H CH₃ 21 22

O NH O O H H CH₃ 23 24

O NH O O H H CH₃ 25 26

O NH O O H H CH₃ 27 28

O NH O O H H CH₃ 29 30

O NH O O H H CH₃ 31 32

O NH O O H H CH₃ 33 34

O NH O O H H CH₃ 35 36

O NH O O H H CH₃ 37 38

O NH O O H H CH₃ 39 40

O NH O O H H CH₃ 41 42

O NH O O H H CH₃ 43 44

O NH O O H H CH₃ 45 46

O NH O O H H CH₃ 47 48

O NH O O H H CH₃ 49 50

O NH O O H H CH₃ 51 52

O NH O O H H CH₃ 53 54

O NH O O H H CH₃ 55 56

O NH O O H H CH₃ 57 58

O NH O O H H CH₃ 59 60

O NH O O H H CH₃ 61 62

O NH O O H H CH₃ 63 64

O NH O O H H CH₃ 65 66

O NH O O H H CH₃ 67 68

O NH O O H H CH₃ 69 70

O NH O O H H CH₃ 71 72

O NH O O H H CH₃ 73 74

O NH O O H H CH₃ 75 76

O NH O O H H CH₃ 77 78

O NH O O H H CH₃ 79 80

O NH O O H H CH₃ 81 82

O NH O O H H CH₃ 83 84

O NH O O H H CH₃ 85 86

O NH O O H H CH₃ 87 88

O NH O O H H CH₃ 89 90

O NH O O H H CH₃ 91 92

O NH O O H H CH₃ 93 94

O NH O O H H CH₃ 95 96

O NH O O H H CH₃ 97 98

O NH O O H H CH₃ 99 100

O NH O O H H CH₃ 101 102

O NH O O H H CH₃ 103 104

O NH O O H H CH₃ 105 106

O NH O O H H CH₃ 107 108

O NH O O H H CH₃ 109 110

O NH O O H H CH₃ 111 112

O NH O O H H CH₃ 113 114

O NH O O H H CH₃ 115 116

O NH O O H H CH₃ 117 118

O NH O O H H CH₃ 119 120

O NH O O H H CH₃ 121 122

O NH O O H H CH₃ 123 124

O NH O O H H CH₃ 125 126

O NH O O H H CH₃ 127 128

O NH O O H H CH₃ 129 130

O NH O O H H CH₃ 131 132

O NH O O H H CH₃ 133 134

O NH O O H H CH₃ 135 136

O NH O O H H CH₃ 137 138

O NH O O H H CH₃ 139 140

O NH O O H H CH₃ 141 142 CH₃CH₂ O NH O O H H CH₃ 143 144

O NH O O H H CH₃ 145 146

O NH O O H H CH₃ 147 148

O NH O O H H CH₃ 149 150

O NH O O H H CH₃ 151 152

O NH O O H H CH₃ 153 154

O NH O O H H CH₃ 155 156

O NH O O H H CH₃ 157 158

O NH O O H H CH₃ 159 160

O NH O O H H CH₃ 161 162

O NH O O H H CH₃ 163 164

O NH O O H H CH₃ 165 166

O NH O O H H CH₃ 167 168

O NH O O H H CH₃ 169 170

O NH O O H H CH₃ 171 172

O NH O O H H CH₃ 173 174

O NH O O H H CH₃ 175 176

O NH O O H H CH₃ 177 178

O NH O O H H CH₃ 179 180

O NH O O H H CH₃ 181 182 183 184 185 186

O NH NCH₃ O NH NCH₃ O O O S S S H H CH₃ 187 188

O NH O O H H H 189 190

O NH O O H CH₃ CH₃ 191 192

O NH O O H H CH₂CH₃ 193 194

O NH O O H H CH₂CH₂CH₃ 195 196

O NH O O CH₃ H CH₃ 197 198

O NH O O H H CH₃ 199 200

O NH O O H H CH₃ 201 202

O NH O O H H CH₃ 203 204

O NH O O H H CH₃ 205 206

O NH O O H H CH₃ 207 208

O NH O O H H CH₃ 209 210

O NH O O H H CH₃ 211 212

O NH O O H H CH₃ 213 214

O NH O O H H CH₃ 215 216

O NH O O H H CH₃ 217 218

O NH O O H H CH₃ 219 220

O NH O O H H CH₃ 221 222

O NH O O H H CH₃ 223 224

O NH O O H H CH₃ 225 226

O NH O O H H CH₃ 227 228

O NH O O H H CH₃ 229 230

O NH O O H H CH₃ 231 232

O NH O O H H CH₃ 233 234

O NH O O H H CH₃ 235 236

O NH O O H H CH₃ 237 238

O NH O O H H CH₃ 239 240

O NH O O H H CH₃

In view of the above, R⁵ may represent hydrogen atom; and R⁶ mayrepresent a C₁-C₂ alkyl group which may optionally be substituted with ahydroxyl group, a hydroxyl group or a C₁-C₂ alkoxy group.

The amide derivatives of the present invention represented by the abovegeneral formula (I) wherein X is R¹(R²)(R³)C—, and Y is an oxygen atom,can be prepared by, for example, the method explained below.

wherein R¹, R², R³, R⁴, R⁵, and R⁶ are the same as those defined above.

A carboxylic acid derivative represented by the above general formula(II) is allowed to react with a condensing agent such asdicyclohexylcarbodiimide, diphenylphospborylazide, carbonyldiimidazole,oxalyl chloride, isobutyl chloroformate, and thionyl chloride,optionally in the presence of a base such as triethylamine and pyridineas required, to activate a carboxylic acid, and then the resultingintermediate is allowed to react with an aniline derivative representedby the above general formula (III), optionally in the presence of a basesuch as triethylamine and pyridine as required, to obtain a compoundrepresented by the above general formula (I). As a solvent used in thecondensation reaction, a stable solvent may be appropriately chosendepending on a type of a condensing agent Reaction conditions may alsobe appropriately chosen so as to be suitable for a condensing agentused.

In the above series of reactions, protection and deprotection of one ormore functional groups may sometimes be required. In such a case, 8protective group suitable for each of the reactive functional group maybe chosen, and reaction procedures can be employed according to knownmethods described in the literature.

The amide derivatives of the present invention represented by the abovegeneral formula (I) wherein X is R⁷—A—, can be prepared by, for example,the method explained below.

wherein R⁷, R⁴, R⁵, and R⁶ are the same as those defined above.

An alcohol derivative represented by the above general formula (IV) isdissolved in an inert solvent such as acetonitrile, methylene chlorideor chloroform, and allowed to be reacted with di(n-succinmidyl)carbonatein the presence of base such as triethylamine or pyridine to obtain anasymmetric carbonate compound (V) as an intermediate. The compound (V)is then dissolved in a polar solvent such as dimethylformamide,N-methylpyrrolidone or dimethylsulfoxide, and allowed to be reacted withthe aniline derivative (VI) in the presence of base such astriethylamine or pyridine to obtain the compound (VII), i.e., thecompound represented by the formula (I) wherein A and Y are an oxygenatom.

wherein R⁷, R⁴, R⁵, R⁶ and Y are the same as those defined above.

The isocyanate derivative (VIII) is dissolved in an inert solvent suchas acetonitrile, methylene chloride or chloroform, and allowed to bereacted with the aniline derivative (VI) to obtain the compound (IX),i.e., the compound represented by the formula (I) wherein A is —NH.

In the above series of reactions, protection and deprotection of one ormore functional groups may sometimes be required. In such a case, aprotective group suitable for each of the reactive functional group maybe chosen, and reaction procedures can be employed according to knownmethods described in the literature.

The compounds of the present invention represented by the above generalformula (I) have excellent antibacterial activity against Helicobacterpylori, and they can exhibit potent antibacterial activity againstHelicobacter pylori in stomach Accordingly, the medicaments of thepresent invention are useful for therapeutic and/or preventive treatmentof various digestive diseases related to the infection caused byHelicobacter pylori, for example, a disease selected from the groupconsisting of gastritis, gastric ulcer, gastric cancer; gastricmalignant lymphoma, MALT lymphoma, duodenal ulcer, and duodenalcarcinoma. More specifically, the compounds may preferably be used asmedicaments for therapeutic treatment of gastritis, gastric ulcer andduodenal ulcer; medicaments for preventive treatment of gastric ulcer,duodenal ulcer, gastric malignant lymphoma, gastric cancer, and duodenalcarcinoma; and medicaments for preventive treatment of recurrence ofgastric ulcer and duodenal ulcer.

As an active ingredient of the medicament of the present invention, oneor more substances selected from the group consisting of the compoundrepresented by the above general formula (I) and a pharmaceuticallyacceptable salt thereof, and a solvate thereof and a hydrate thereof canbe used. The medicament of the present invention may preferably beprovided in the form of a pharmaceutical composition comprising theabove substance as an active ingredient and one or more pharmaceuticallyacceptable additives for pharmaceutical preparations. In thepharmaceutical compositions, a ratio of the active ingredient to thepharmaceutical additive may be about 1% by weight to about 90% byweight.

The medicament of the present invention may be administered as apharmaceutical composition for oral administration such as granules,subtilized granules, powders, hard capsules, soft capsules, syrups,emulsions, suspensions, and liquid drugs, or administered as apharmaceutical composition for parenteral administration such asinjections for intravenous, intramuscular or subcutaneousadministration, drip infusions, and suppositories. A preparationprepared as a powdery pharmaceul composition may be dissolved before useand used as an injection or a drip infusion.

Solid or liquid pharmaceutical additives may be used for preparation ofthe pharmaceutical compositions. The pharmaceutical additives may beeither organic or inorganic materials. Examples of excipients used formanufacturing solid preparations include, for example, lactose, sucrose,starch, talc, cellulose, dextrin, china clay, and calcium carbonate. Forthe manufacture of liquid formulations for oral admintation such asemulsions, syrups, suspensions, and liquids, for example, ordinary inertdiluents such as water and vegetable oils may be used. In addition tothe inert diluents, auxiliaries such as, for example, moistening agents,suspending aids, sweetening agents, aromatics, colorants, preservativesand the like may be formulated. Liquid preparations may be filled incapsules after their preparation that are made of an absorbable materialsuch as gelatin. Examples of solvents or su spending mediums used forthe manufacture of pharmaceutical preparations for parenteraladministration such as injections and suppositories include, forexample, water, propylene glycol, polyethylene glycol, berzyl alcohol,ethyl oleate, lecithin and the like. Examples of base materials used forpreparation of suppositories include, for example, cacao butter,emulsified cacao butter, lauric lipid, Witepsol and the like. Methodsfor manufacturing the pharmaceutical preparations are notparticularlylimited, and any methods ordinarily used in the art may be employed.

A dose of the medicament oft he present invention may generally be fromabout 0.01 to 5,000 mg per day for an adult based on the weight of thecompounds of the present invention. However, it is preferred to suitablyincrease or decreased depending on age. conditions, symptoms or other ofa patient The daily dose may be administered once a day or twice tothree times a day with suitable intervals, or alternatively,intermittently administered with intervals of several days. When used asan injection, a dose of the medicaments of the present invention may beabout 0.001 to 100 mg per day for an adult based on the weight of thecompounds of the present invention.

EXAMPLES

The present invention will be explained more specifically by referringto the following examples. However, the scope of the present inventionis not limited to these examples.

Example 1 Preparation ofN-(3-methylcarbamoylphenyl)-3-chlorophenylacetamide (Compound No. 17 inTable 1)

3-Chlorophenylacetic acid (192 mg) was dissolved in methylene chloride(8 ml), and oxalyl chloride (0.10 ml) and one drop of dimethylformamidewere added to the solution. After stirring for 1 hour at roomtemperature, 3-aminobenzoylmethyide (167 mg) and pyridine (0.19 ml) wereadded to the reaction mixture, and then stirred at room temperatureovernight. After the solvent was evaporated under reduced pressure,water (10 ml) and 2N aqueous hydrochloric acid (1 ml) were added to theresidue, and the deposited crystals were collected by filtration andwashed with water. These crystals were dried and added in ethyl acetate(6 ml), and then the mixture was heated under reflux for ten minutes.The mixture was cooled to room temperature, and the crystals werecollected by filtration and washed with ethyl acetate to obtain thedesired compound (233 mg, yield 68%).

Melting point; 165-166° C.; IR (KBr, cm⁻¹): 3324, 1642, 1593, 1555; NMR(DMSO-d₆, δ): 2.76 (d, J=4.5 Hz, 3H), 3.68(s, 2H), 7.26-7.42 (m, 5H),7.48 (d, J=7.8 Hz, 1H), 7.74 (d, J=7.8 Hz, 1H), 8.02 (dd, J=1.8 Hz, 1.8Hz, 1H), 8.36 (d, J=4.5 Hz, 1H), 10.31 (s, 1H).

In similar manners to the method of Example 1, compounds of Examples2-50 were prepared. Their physicochemical properties are set out below.

Example 2 Preparation of N-(3-Methylcarbamoylphenyl)cyclohexylacetamide(Compound No. 4 in Table 1)

Melting point: 183° C.; IR (KBr, cm⁻¹): 3293, 1657, 1640, 1588, 1535;NMR (DMSO-d₆, δ); 0.99 (m, 2H), 1.03-1.38 (m, 3H), 1.55-1.90 (m, 6H),2.19 (d, J=7.0 Hz, 2H), 2.76 (d, J=4.5 Hz, 3H), 7.34 (dd, J=7.8 Hz, 7.8Hz, 1H), 7.45 (d, J=7.8 Hz, 1H), 7.74 (d, J=7.8 Hz, 1H), 8.01 (s, 1H),8.34 (d, J=4.5 Hz, 1H), 9.95 (s, 1H).

Example 3 Preparation of N-(3-Methylcarbamoylphenyl)phenylacetamide(Compound No. 7 in Table 1)

Melting point; 140-142° C.; NMR (DMSO-d₆, δ): 2.75 (d, J=4.5 Hz, 3H),3.63 (s, 2H), 7.22-7.48 (m, 7H), 7.74 (m, 1H), 8.01 (s, 1H), 8.37 (d,J=4.5 Hz, 1H), 10.30 (s, 1H).

Example 4 Preparation ofN-(3-Methylcarbamoylphenyl)-1-phenylcyclopentanecarboxamide (CompoundNo. 11 in Table 1)

Melting point: 147° C.; IR (KBr, cm⁻¹): 3339, 3275, 1638, 1586, 1557,1528; NMR (DMSO-d₆, δ): 1.67 (m, 4H), 1.94 (m, 2H), 2.65 (m, 2H), 2.75(d, J=4.5 Hz, 3H, 7.20-7.60 (m, 7H), 7.76 (d, J=7.2 Hz, 1H), 7.98 (s,1H), 8.33 (d, J=4.5 Hz, 1H), 9.32 (s, 1H).

Example 5 Preparation ofN-(3-Methylcarbamoylphenyl)-3-fluorophenylacetamide (Compound No. 14 inTable 1)

Melting point: 147-148° C.; IR (KBr, cm⁻¹): 3314, 1661, 1636, 1587,1530; NMR (DMSO-d₆, δ): 2.76 (d, J=4.2 Hz, 3H), 3.69 (s, 2H), 7.08 (dd,J=5.7Hz, 5.7 Hz, 1H), 7.14 (d, J=7.5 Hz, 2H), 7.38 (m, 2H), 7.47 (d,J=8.1 Hz, 1H), 7.74 (d, J=8.1 Hz, 1H), 8.02 (s, 1H), 8.35 (d, J=4.2 Hz,1H), 10.30 (s, 1H).

Example 6 Preparation ofN-(3-Methylcarbamoylphenyl)-4-fluorophenylacetamide (Compound No. 15 inTable 1)

Melting point: 155-156° C.; IR (KBr, cm⁻¹): 3293, 1657, 1634, 1588,1535, 1512; NMR (DMSO-d₆, δ): 2.76 (d, J=3.9 Hz, 3H), 3.65 (s, 2H), 7.15(dd, J=9.0 Hz, 9.0Hz, 2H), 7.25-7.41 (m, 3H), 7.47 (d, J=7.5 Hz, 1H),7.75 (d, J=8.1 Hz, 1H), 8.02 (s, 1H), 8.35 (d, J=3.9 Hz, 1H), 10.28 (s,1H).

Example 7 Preparation ofN-(3-Methylcarbamoylphenyl)-2-chlorophenylacetamide (Compound No. 16 inTable 1)

Melting point: 211-212° C.; IR (KBr, cm⁻¹): 3268, 1659, 1642, 1586,1535; NMR (DMSO-d₆, δ): 2.77 (d, J=3.6 Hz, 3H), 3.85 (s, 2H), 7.25-7.55(m, 6H), 7.74 (d, J=7.5 Hz, 1H), 8.04 (s, 1H), 8.36 (d, J=3.6 Hz, 1H,10.34 (s, 1H).

Example 8 Preparation ofN-(3-Methylcarbamoylphenyl)-4-chlorophenyltamide (Compound No. 18 inTable 1)

Melting point: 163-164° C.; IR (KBr, cm⁻¹): 3279, 1663, 1640, 1588,1535; NMR (DMSO-d₆, δ): 2.76 (d, J=3.9 Hz, 3H), 3.66 (s, 2H), 7.35-7.42(m, 5H), 7.47 (d, J=7.8 Hz, 1H), 7.75 (d, J=7.8 Hz, 1H), 8.02 (dd, J=1.5Hz, 1.5 Hz, 1H), 8.36 (d, J=3.9 Hz, 1H), 10.30 (s, 1H).

Example 9 Preparation of N-(3-Carbamoylphenyl)-3-bromophenylacetamide(Compound No. 20 in Table 1)

Melting point: 202° C.; IR (KBr, cm⁻¹): 3378, 3295, 1659, 1624, 1586,1534; NMR (DMSO-d₆, δ): 3.67 (s, 2H), 7.20-7.60 (m, 7H), 7.76 (d, J=9.3Hz, 1H), 7.94 (s, 1H), 8.03 (s, 1H), 10.33 (s, 1H).

Example 10 Preparation ofN-(3-Methylcarbamoylphenyl)-3-bromophenylacetamide (Compound No. 22 inTable 1)

Melting point: 176-178° C.; IR (KBr, cm⁻¹): 3324, 3254, 1642, 1591,1554; NMR (DMSO-d₆, δ): 2.76 (d, J=4.5 Hz, 3H), 3.68 (s, 2H), 77.27-7.41(m, 3H), 7.45-7.50 (m, 2H), 7.56 (s, 1H), 7.75 (d, J=8.0 Hz 1H), 8.03(s, 1H), 8.42 (d, J=4.5 Hz, 1H) 10.35 (s, 1H).

Example 11 Preparation ofN-(3-Dimethylcarbamoylphenyl-3-bromophenylacetamide (Compound No. 23 inTable 1)

Melting point 119-120° C.; IR (KBr, cm⁻¹): 1678, 1613, 1588, 1557; NMR(DMSO-d₆, δ): 2.90 (s, 3H), 2.96 (s, 3H), 3.68 (s, 2H), 7.06 (d, J=7.8Hz, 1H), 7.25-7.41 (m, 3H), 7.47 (m, 1H), 7.53-7.60 (m, 2H), 7.68 (s,1H, 10.30 (s, 1H).

Example 12 Preparation ofN-(3-Ethylcarbamoylphenyl)-3-bromophenylaetamide (Compound No. 24 inTable 1)

Melting point: 155° C.; IR (KBr, cm⁻¹): 3329, 3268, 1665, 1640, 1549;NMR (DMSO-d₆, δ): 1.11 (t, J=6.9 Hz, 3H), 3.29 (m, 2H), 3.67 (s, 2H,7.20-7.40 (m, 3H), 7.47 (d, J=8.1 Hz, 1H), 7.49 (d, J=8.1 Hz, 1H), 7.56(s, 1H), 7.75 (d, J=8.4 Hz, 1H), 8.00 (s, 1H), 8.41 (t, J=5.1 Hz, 1H),10.32 (s, 1H).

Example 13 Preparation ofN-(3-(2-Hydroxyethyl)carbamoylphenyl)-3-bromophenylacetamide (CompoundNo. 28 in Table 1)

Melting point: 202° C.; IR (KBr, cm⁻¹): 3407, 3358, 3279, 1671, 1640,1589, 1539; NMR (DMSO-d₆, δ): 3.26 (m, 2H), 3.47 (m, 2H), 3.65 (s, 2H),4.67 (t, J=5.7 Hz, 1H), 7.20-7.60 (m, 6H), 7.73 (d, J=7.2 Hz, 1H), 7.99(s, 1H), 8.32 (m, 1H), 10.28 (s, 1H).

Example 14 Preparation ofN-(3-Hydroxycarbamoylphenyl)-3-bromophenylacetamide (Compound No. 29 inTable 1)

Melting point: 184-186° C. (decompoition); IR (KBr, cm⁻¹): 3314, 3231,1663, 1632, 1582, 1535; NMR (DMSO-d₆, δ): 3.68(s, 2H), 7.25-7.60 m, 6H),7.75 (d, J=6.9 Hz, 1H), 7.98 (s, 1H), 9.01 (s, 1H), 10.33 (s, 1H), 11.12(s, 1H).

Example 15 Preparation ofN-(Methoxycarbamoylphenyl)-3-bromophenylacetamide (Compound No. 30 inTable 1)

Melting point: 166° C.; IR (KBr, cm⁻¹): 3299, 3187, 1659, 1611, 1595,1560; NMR (DMSO-d₆, δ): 3.69 (s, 5H), 7.22-7.60 (m, 6H), 7.77 (s, 1H),8.00 (s, 1H), 10.37 (s, 1H), 11.69 (s, 1H).

Example 16 Preparation ofN-(3-Methylcarbamoylphenyl)-4-bromophenylacetamide (Compound No. 33 inTable 1)

Melting point; 165-166° C.; IR (KBr, cm⁻¹): 3283, 1665, 1642, 1588,1534; NMR DMSO-d₆, δ): 2.77 (d, J=4.5 Hz, 3H), 3.64 (s, 2H), 7.23-7.40(m, 3H), 7.40-7.58 (m, 3H), 7.75 (d, J=7.8 Hz, 1H), 8.01 (s, 1H), 8.37(d, J=4.5 Hz, 1H), 10.30 (s, 1H).

Example 17 Preparation ofN-(3-Methylcarbamoylphenyl)-3-methylphenylacetamide (Compound No. 42 inTable 1)

Melting point: 131° C.; IR (KBr, cm⁻¹): 3299, 1659, 1634, 1586, 1530;NMR (DMSO-d₆, δ): 2.29 (s, 3H), 2.76 (d, J=4.5 H 3H), 3.60 (s, 2H), 7.06(d, J=6.9 Hz, 1H), 7.09-7.22 (m, 3H), 7.36 (dd, J=7.8 Hz, 7.8 Hz, 1H),7.47 (d, J=7.8 Hz, 1H), 7.75 (d, J=7.8 Hz, 1H), 8.02 (s, 1H), 8.35 (d,J=4.5 Hz, 1H), 10.26 (s, 1H).

Example 18 Preparation ofN-(3-Methylcarbamoylphenyl)-4-methylphenylacetamide (Compound No. 43 inTable 1)

Melting point: 174-175° C.; IR (KBr, cm⁻¹): 3339, 3296, 1659, 1639,1586, 1528; NMR (DMSO-d₆, δ): 2.27 (s, 3H), 2.76 (d, J=4.5 Hz, 3H), 3.59(s, 2H), 7.12 (d, J=8.1 Hz, 2H), 7.22 (d, J=8.1 Hz, 2H), 7.36 (dd, J=7.8Hz, 7.84 Hz), 7.47 (d, J=7.8 Hz, 1H), 7.55 (d, J=7.8 Hz, 1H), 8.01 (s,1H), 8.35 (d, J=4.5 Hz, 1H), 10.24 (s, 1H).

Example 19 Preparation ofN-(3-Methylcarbamoylphenyl)-3-methoxyphenylacetamide (Compound No. 59 inTable 1)

Melting point: 104-106° C.; NM (DMSO-d₆, δ): 2.76 (d, J=4.5 Hz, 3H),3.60 (s, 2H), 3.73 (m, 3H), 6.81 (m, 1H), 6.89-6.92 (m, 2H), 7.23 (m,2H), 7.36 (m, 1H), 7.47 (m, 1H), 7.76 (m, 1H), 8.02 (s, 1H), 8.38 (m,1H), 10.28 (s, 1H).

Example 20 Preparation ofN-(3-Methylcarbamoylpbenyl)-4-methoxyphenylacetamide (Compound No. 60 inTable 1)

Melting point: 155-157° C.; NMR (DMSO-d₆, δ): 2.75 (d, J=4.5 Hz 3H),3.55 (s, 2H), 3.71 (s, 3H), 6.88 (d, J=8.8 Hz, 2H), 7.24 (d, J=8.8 Hz,2H), 7.35 (m, 1H), 7.45 (d, J=7.8 Hz, 1H), 7.74 (d, J=7.8 Hz, 1H), 8.00(s, 1H), 8.37 (m, 1H), 10.24 (s, 1H).

Example 21 Preparation ofN-(3-Methylcarbamoylphenyl)-3,4-dimethoxyphenylacetamide (Compound No.61 in Table 1)

NMR DMSO-d₆, δ): 2.75 (d, J=4.5 Hz, 3H), 3.55 (s, 2H), 3.71 (s, 3H),3.73 (s, 3H), 6.82-6.94 (m, 3H), 7.35 (m, 1H), 7.46 (d, J=7.8 Hz, 1H),7.75 (d, J=7.8 Hz, 1H), 8.00 (s, 1H), 8.37 (m, 1H), 10.22 (s, 1H).

Example 22 Preparation ofN-(3-Methylcarbamoylphenyl)-3,5-dimethoxyphenylacetamide (Compound No.62 in Table 1)

Melting point: 146-147° C.; IR (KBr, cm⁻¹): 3341, 3246, 1667, 1638,1589, 1547; NMR DMSO-d₆, δ): 2.76 (d J=4.2 Hz, 3H), 3.56 (s, 2H), 3.73(s, 6H), 6.39 (s, 1H), 6.51 (s, 2H), 7.36 (dd, J=7.8 Hz, 7.8 Hz 1H),7.47 (d, J=7.8 Hz, 1H), 7.75 (d, J=7.8 Hz, 1H), 8.01 (s, 1H), 8.35 (d,J=4.2 Hz, 1H), 10.23 (s, 1H).

Example 23 Preparation ofN-(3-Methylcarbamoylphenyl)-3,4,5-trimethoxyphenylacetamide (CompoundNo. 63 in Table 1)

Melting point: 81-82° C.; IR (KBr, cm⁻¹): 3304, 1642, 1589, 1554, 1508;NMR (DMSO-₆, δ): 2.76 (d, J=4.5 Hz, 3H), 3.57 (s, 2H), 3.63 (s, 3H),3.77 (s, 6H), 6.66 (s, 2H), 7.39 (dd, J=7.8 Hz, 7.8 Hz, 1H), 7.47 (d,J=7.8 Hz, 1H), 7.76 (d, J=7.8 Hz, 1H, 8.03 (s, 1H), (s, 1H), 8.37 (d,J=4.5 Hz, 1H), 10.23 (s, 1H).

Example 24 Preparation ofN-(3-Methylcarbamoylphenyl)-3-benzyloxyphenylacetamide (Compound No. 68in Table 1)

Melting point: 150° C.; IR (KBr, cm⁻¹): 3302, 1661, 1634, 1586, 1530;NMR (DMSO-d₆, δ): 2.76 (d, J=4.5 Hz, 3H), 3.61 (s, 2H), 5.09 (s, 2H),6.91 (dd, J=7.8 Hz, 7.8 Hz, 2H), 7.01 (s, 1H), 7.27 (dd, J=7.8 Hz,7.8Hz, 1H), 7.25-7.52 (m, 7H), 7.74 (d, J=7.8 Hz, 1H), 8.02 (s, 1H),8.36 (d, J=4.5 Hz, 1H), 10.27 (s, 1H).

Example 25 Preparation of N-(3-Carbamoylphenyl)-3-hydroxyphenylacetamide(Compound No. 71 in Table 1)

Melting point: 188-189° C.; NMR (DMSO-d₆, δ): 3.52 (s, 2H), 6.62 (m,1H), 6.72-6.75 (m, 2H), 7.08 (m, 1H), 7.32-7.37 (m, 2H, 7.51 (d, J=6.9Hz, 1H), 7.76 (d, J=7.8 Hz, 1H), 7.92 (s 1H), 8.02 (s, 1H), 9.34 (s,1H), 10.25 (s, 1H).

Example 26 Preparation ofN-(3-Methylcarbamoylphenyl)-3-hydroxyphenylacetamide (Compound No. 72 inTable 1)

Melting point: 163° C.; IR (KBr, cm⁻¹): 3333, 3293. 1676, 1640, 1588,1562; NMR (DMSO-d₆, δ): 2.74 (d, J=4.2 Hz, 3H), 3.53 (s, 2H), 6.61 (d,J=7.2 Hz, 1H), 6.72 (d, J=7.2Hz, 1H), 6.74 (s, 1H), 7.08 (dd, J=7.2 Hz,7.2Hz, 1H), 7.34 (dd, J=7.8 Hz, 7.8 Hz, 1H), 7.45 (d, J=7.8 Hz, 1H),7.73 (d, J=7.8 Hz, 1H), 7.80 (s, 1H), 8.34 (d, J=4.2 Hz, 1H), 9.30 (s,1H), 10.22 (s, 1H).

Example 27 Preparation ofN-(3-Methylcarbamoylphenyl)-4-hydroxyphenylacetamide (Compound No. 73 inTable 1)

Melding point: 195-196° C.; IR (KBr, cm⁻¹): 3393, 3283, 1661, 1638,1541, 1518; NMR (DMSO-d₆, δ): 2.73 (d, J=4.5 Hz, 3H), 3.48 (s, 2H), 6.68(d, J=8.4 Hz, 2H), 7.10 (d, J=8.4 Hz, 2H), 7.33 (dd, J=7.8 Hz, 7.8 Hz,1H), 7.43 (d, J=8.7 Hz, 1H), 7.72 (d, J=7.8 Hz, 1H), 7.98 (s, 1H), 8.32(d, J=4.5 Hz, 1H), 9.20 (s, 1H), 10.14 (s, 1H).

Example 28 Preparation ofN-(3-methylcarbonylphenyl)-3-nitrophenylatamide (Compound No. 74 inTable 1)

Melting point: 139° C.; IR (KBr, cm⁻¹): 3322, 3250, 1665, 1640, 1666,1624; NMR (DMSO-d₆, δ): 2.76 (d, J=4.5 Hz, 3H), 3.86 (s, 2H), 7.37 (dd,J=7.8 Hz, 7.8 Hz, 1H), 7.49 (d, J=7.8 Hz, 1H), 7.64 (dd, J=8.1 Hz, 8.1Hz, 1H), 7.75 (d, J=8.1 Hz, 1H), 7.80 (d, J=8.1 Hz, 1H), 8.03 (s, 1H),8.13 (d, J=8.1 Hz, 1H), 8.24 (s, 1H), 8.37 (d, J=4.5 Hz, 1H), 10.39 (s,1H).

Example 29 Preparation ofN-(3-Methylcarbamoylphenyl)-4-nitrophenylacetamide (Compound No. 75 inTable 1)

Melting point: 148-151° C.; IR (KBr, cm⁻¹): 3277, 1663, 1640, 1588,1522; NMR (DMSO-d₆, δ): 274 (d, J=4.2 Hz, 3H), 3.83 (s, 2H), 7.35 (dd,J=7.8 Hz, 7.8 Hz, 1H), 7.45 (m, 1H), 7.60 (d, J=8.7 Hz, 2H), 7.72 (d,J=8.4 Hz, 1H), 8.00 (s, 1H), 8.19 (d, J=8.7 Hz, 2H), 8.33 (d, J=4.2 Hz,1H), 10.36 (s, 1H.

Example 30 Preparation ofN-(3-Methylcarbamoylphenyl)-1-naphthylacetamide (Compound No. 113 inTable 1)

Melting point: 201-202° C.; IR (KBr, cm⁻¹): 3274, 1657, 1640, 1588,1532; NMR (DMSO-d₆, δ): 2.75 (d, J=4.5 Hz, 3H, 4.16 (s, 2H), 7.36 (dd,J=8.1 Hz, 8.1 Hz, 1H), 7.40-7.60 (m, 5H), 7.74 (d, J=7.8 Hz, 1H), 7.84(d, J=7.8 Hz, 1H), 7.97 (d, J=7.8 Hz, 1H), 8.03 (s, 1H), 8.35 (d, J=7.8Hz, 1H), 8.37 (d, J=4.5 Hz, 1H), 10.44 (s, 1H).

Example 31 Preparation of N-(3-Methylcarbamoylphenyl)-2-naphthylacetnide(Compound No. 114 in Table 1)

Melting point: 175-176° C.; IR (KBr, cm⁻¹): 3393, 1655, 1634, 1588,1530; NMR DMSO-d₆, δ): 2.76 (d, J=4.5 Hz, 3H), 3.83 (s, 2H), 7.37 (dd,J=7.8 Hz, 7.8 Hz, 1H), 7.40-7.55 (m, 4H, 7.77 (d, J=8.4 Hz, 1H),7.81-7.96 (m, 4H), 8.04 (s, 1H), 8.36 (d, J=4.5 Hz, 1H), 10.37 (s, 1H).

Example 32 Preparation of N-(3-Methylcarbamoylphenyl-3-indolylacetamide(Compound No. 140 in Table 1)

Melting point: 168-169° C.; IR (KBr, cm⁻¹): 3382, 3287, 1655, 1636,1588, 1565, 1528; NMR (DMSO-d₆, δ): 2.73 (d, J=4.5 Hz 3H), 3.72 (s, 2H),6.96 (dd, J=7.5 Hz, 7.5 Hz, 1H), 7.05 (dd, J=7.8 Hz, 7.8 Hz, 1H), 7.24(s, 1H), 7.27-7.38 (m, 2H), 7.43 (d, J=7.8 Hz, 1H), 7.59 (d, J=7.8 Hz,1H, 7.75 (d, J=8.7 Hz, 1H), 8.00 (s, 1H), 8.32 (d, J=4.5 Hz, 1H), 10.18(s, 1H), 10.88 (s, 1H).

Example 33 Preparation ofN-(3-Methylcarbamoylphenyl)-3-benzothienylacetamide (Compound No. 146 inTable 1)

Melting point: 194° C.; IR (KBr, cm⁻¹): 3285, 1663, 1636, 1588, 1532;NMR (DMSO-d₆, δ): 2.75 (d, J=4.2 Hz, 3H), 3.94 (s, 2H), 7.32-7.53 (m,4H), 7.61 (s, 1H), 7.76 (d, J=6.9 Hz, 1H), 7.91 (d, J=7.2 Hz, 1H), 7.98(d, J=7.2 Hz, 1H), 8.04 (s, 1H), 8.35 (d, J=4.2 Hz, 1H), 10.40 (s, 1H).

Example 34 Preparation ofN-(3-Methylcarbamoylphenyl)-4-benzothienylacetamide (Compound No. 148 inTable 1)

Melting point: 192° C.; IR (KBr, cm⁻¹): 3295, 1676, 1632, 1595, 1559;NMR (DMSO-d₆, δ): 2.76 (d, J=4.2 Hz, 3H), 4.03 (s, 2H), 7.30-7.41 (m,3H), 7.47 (d, J=7.8 Hz, 1H), 7.65 (d, J=5.4 Hz, 1H), 7.75 (d, J=6.3 Hz,1H), 7.77 (d, J=5.4 Hz, 1H), 7.91 (m, 1H), 8.02 (s, 1H), 8.35 (d, J=4.2Hz, 1H), 10.39 (s, 1H).

Example 35 Preparation ofN-(3-Methylcarbamoylphenyl)-2,2-dimethyl-2,3-dihydro-5-benzofuranylacetamide(Compound No. 157 in Table 1)

Melting point: 92-93° C.; IR (KBr, cm⁻¹): 3289, 1665, 1611, 1589, 1555;NMR (DMSO-d₆, δ): 1.39 (s, 6H), 1.53 (s, 6H), 2.75 (d, J=4.5 Hz, 3H),2.99 (s, 2H), 6.65 (d, J=8.4 Hz, 1H), 7.05 (d, J=8.1 Hz, 1H), 7.18 (s,1H), 7.34 (dd, J=7.8 Hz, 7.8 Hz, 1H), 7.45 (d, J=7.5 Hz, 1H), 7.80 (d,J=7.8 Hz, 1H), 8.02 (s, 1H), 8.33 (d, J=4.5 H, 1H), 9.18 (s, 1H).

Example 36 Preparation ofN-(3-Methylcarbamoylphenyl)-3,4-methylenedioxyphenyl-acetamide (CompoundNo. 159 in Table 1)

Melting point: 174-175° C.; IR (KBr, cm⁻¹): 3337, 3291, 1659, 1634,1586, 1530, 1505; NMR (DMSO-d₆, δ): 2.76 (d, J=4.5 Hz, 3H), 3.55 (s,2H), 5.98 (s, 2H), 6.74-6.93 (m, 3H), 7.36 (dd, J=7.8 Hz, 7.8 Hz, 1H),7.47 (d, J=7.8 Hz, 1H), 7.75 (d, J=7.8 Hz 1H), 8.01 (s, 1H), 8.35 (d,J=4.5 Hz, 1H), 10.20 (s, 1H).

Example 37 Preparation of N-(3-Methylearbamoylphenyl)phenoxyacetaride(Compound No. 176 in Table 1)

Melting point: 131° C.; IR (KBr, cm⁻¹): 3378, 3283, 1669, 1640, 1588,1535; NMR (DMSO-d₆, δ): 2.75 (d, J=4.5 Hz, 3H), 4.69 (s, 2H), 6.63-7.01(m, 3H), 7.22-7.40 (m, 3H), 7.50 (d, J=7.8 Hz, 1H), 7.77 (d, J=7.8 Hz,1H), 8.05 (s, 1H), 8.36 (d, J=4.5 Hz, 1H), 10.18 (s, 1H).

Example 38 Preparation ofN-(3-Methylcarbamoylphenyl)-2-chlorophenoxyacetamide (Compound No. 177in Table 1)

Melting point: 172-173° C.; IR (KBr, cm⁻¹): 3385, 3297, 1688, 1640,1591, 1549; NMR (DMSO-d₆, δ): 2.77 (d, J=4.5 Hz, 3H), 4.85(s, 2H), 6.99(dd, J=7.5 Hz, 7.5 Hz, 1H), 7.08 (d, J=8.1 Hz, 1H), 7.30 (dd, J=7.5 Hz,7.5 Hz, 1H), 7.38-7.60 (m, 3H), 7.76 (d, J=8.4 Hz, 1H), 8.06 (s, 1H),8.42 (d, J=4.5 Hz, 1H), 10.31 (s, 1H).

Example 39 Preparation ofN-(3-Methylcarbamoylphenyl)-2-methylphenoxyacetamide (Compound No. 183in Table 1)

Melting point: 148° C.; IR (KBr, cm⁻¹): 3399, 3285, 1656, 1640, 1547;NMR (DMSO-d₆, δ): 2.24 (s, 3H), 2.75 (d, J=4.5 Hz, 3H), 4.70 (s, 2H),6.80-6.90 (m, 2H), 7.07-7.19 (m, 2H), 7.37 (dd, J=8.1 Hz, 7.8 Hz, 1H),7.49 (d, J=7.8 Hz, 1H), 7.75 (d, J=8.1 Hz, 1H), 8.05 (s, 1H), 8.35 (d,J=4.5 Hz, 1H), 10.14 (s, 1H).

Example 40 Preparation ofN-(3-Methylcarbamoylphenyl)-2-methoxyphenoxyacetamide (Compound No. 187in Table 1)

Melting point: 133° C.; IR (KBr, cm⁻¹): 3385, 3268, 1690, 1638, 1591,1547; NMR (DMSO-d₆, δ): 2.75 (d, J=4.5 Hz, 3H), 3,79 (s, 3H), 4.66 (s,2H), 6.82-7.02 (m, 4H), 7.38 (dd, J=7.8 Hz, 7.8 Hz, 1H), 7.49 (d, J=7.8Hz, 1H, 7.75 (d, J=7.8 Hz, 1H, 8.05 (s, 1H), 8.38 (d, J=4.5 Hz, 1H),10.18 (s, 1H).

Example 41 Preparation ofN-(3-Methylcarbamoylphenyl)-1-naphthyloxyacetamide (Compound No. 191Table 1)

Melting point: 194° C.; IR (KBr, cm⁻¹): 3405, 3304, 1696, 1638, 1541;NMR (DMSO-₆, δ): 2.75 (d, J=4.2 Hz, 3H), 4.92 (s, 2H, 6.92 (d, J=7.8 Hz,1H), 7.33-7.62 (m, 6H), 7.79 (d, J=8.1 Hz, 1H), 7.88 (m, 1H), 8.08 (s,1H), 8.31 (m, 1H), 8.41 (d, J=4.2 Hz, 1H), 10.36 (s, 1H).

Example 42 Preparation ofN-(3-Methylcarbamoylphenyl)-2-naphthyloxyacetamide (Compound No. 192 inTable 1)

Melting point: 174° C.; IR (KBr, cm⁻¹): 3382, 3275, 1672, 1638, 1588,1557, 1534; NMR (DMSO-d₆, δ): 2.75 (d, J=4.5 Hz, 3H), 4.82 (s, 2H),7.22-7.58 (m, 6H), 7.78-7.95 (m, 4H), 8.09 (s, 1H), 8.40 (d, J=4.5 Hz,1H), 10.28 (s, 1H).

Example 43 Preparation ofN-(3-Methylcarbamoylphenyl)-2,3-dichlorophenoxyacetamide (Compound No.204 in Table 1)

Melting point: 192-193° C.; IR (KBr, cm⁻¹): 3385, 3291, 1692, 1644,1547; NMR (DMSO-d₆, δ): 2.77 (d, J=4.5 Hz 3H), 4.91 (s 2H), 7.08 (d,J=8.1 H, 1H), 7.20-7.45 (m, 3H), 7.52 (d, J=7.8 Hz, 1H), 7.74 (d, J=8.7Hz, 1H), 8.05 (s, 1H), 8.42 (d, J=4.5 Hz, 1H), 10.34 (s, 1H).

Example 44 Preparation ofN-(3-Methylcarbamoylphenyl)-2-methyl-1-naphthylacetamide (Compound No.216 in Table 1)

Melting point: 230-231° C.; IR (KBr, cm⁻¹): 3299, 3071, 1684, 1638,1589, 1560; NMR (DMSO-d₆, δ): 2.50 (s, 3H), 2.73 (d, J=4.5 Hz, 3H), 4.21(s, 2H), 7.22-7.55 (m, 5H), 7.65-7.78 (m, 2H), 7.85 (d, J=7.8 Hz, 1H),8.01-8.15 (m, 2H), 8.36 (d, J=4.5 Hz, 1H), 10.50 (s, 1H),

Example 45 Preparation ofN-(3-Methylcarbamoylphenyl)-2-hydroxy-1-naphthylacetamide (Compound No.219 in Table 1)

Melting point: 229-230° C.; IR (KBr, cm⁻¹): 3310, 1686, 1613, 1582,1661; NMR (DMSO-d₆, δ): 2.75 (d, J=4.2 Hz, 3H), 4.11 (s, 2H), 7.19 (d,J=9.0 Hz, 1H), 7.20-7.50 (m, 4H), 7.66-7.82 (m, 3H), 7.87 (d, J=8.4 Hz,1H), 8.04 (s, 1H), 8.37 (d, J=4.5 Hz, 1H), 9.79 (s, 1), 10.32 (s, 1H).

Example 46 Preparation ofN-(3-Methylcarbamoylphenyl)-3-phenylpropionamide (Compound No. 233 inTable 1)

Melting point; 142-143° C.; IR (KBr, cm⁻¹): 3295, 1657, 1613, 1593,1545; NMR (DMSO-d₆, δ): 2.62 (t, J=7.8 Hz, 2H), 2.75 (d, J=4.5 Hz, 3H),2.90 (t, J=7.8 Hz, 2H), 7.10-7.40 (m, 6H), 7.44 (d, J=7.5 Hz, 1H), 7.72(d, J=7.5 Hz, 1H), 7.99 (s, 1H), 8.33 (d, 4.5 Hz, 1H), 10.00 (s, 1H).

Example 47 Preparation ofN-(3-Methylcarbamoylphenyl)-3-(2-methylphenyl)propionamide (Compound No.240 in Table 1)

Melting point: 131° C.; IR (KBr, cm⁻¹): 3289, 1674, 1640, 1555; NMR(DMSO-d₆, δ): 2.29 (s, 3H, 2.57 (t, J=7.8 Hz, 2H), 2.75 (d, J=4.2 Hz,3H), 2.88 (t, J=7.8 Hz, 2H), 7.02-7.18 (m, 4H), 7.34 (dd, J=7.8 Hz, 7.2Hz, 1H), 7.44 (d, J=7.2 Hz, 1H), 7.73 (d, J=7.8 Hz, 1H), 7.98 (s, 1H),8.33 (d, J=4.2 Hz 1H), 10.01 (s, 1H).

Example 48 Preparation ofN-(3-Methylcarbamoylphenyl)-3-(4-hydroxyphenyl)propionamide (CompoundNo. 246 in Table 1)

Melting point: 158° C.; IR (KBr, cm⁻¹): 3424, 3285, 1647, 1553; NMR(DMSO-d₆, δ): 2.54 (t J=7.8 Hz, 2H), 2.74 (d, J=4.2 Hz 3H), 2.78 (t,J=7.8 Hz, 2H), 6.64 (d, J=8.1 Hz, 2H), 7.01 (d, J=8.1 Hz, 2H), 7.33 (dd,J=8.1 Hz, 7.5 Hz, 1H), 7.43 (d, J=7.5 Hz, 1H), 7.71 (d, J=8.1 Hz, 1H),7.98 (s, 1H, 8.32 (d, J=4.2 Hz, 1H), 9.10 (s, 1H), 9.97 (s, 1H).

Example 49 Preparation ofN-(3-Methylcarbamoylphenyl)-3-(2-methoxyphenyl)propienamide (CompoundNo. 246 in Table 1)

Melting point: 150° C.; IR (KBr, cm⁻¹): 3297, 1658, 1644, 1550; NMR(DMSO-d₆, δ): 2.56 (t, J=7.2 Hz, 2H), 2.75 (d, J=3.9 Hz, 3H), 2.85 (t,J=7.2 Hz, 2H), 3.78 (s, 3H), 6.84 (dd, J=7.5 Hz, 7.5 Hz, 1H), 6.93 (d,J=7.5 Hz, 1H), 7.05-7.20 (m, 2H), 7.26 (dd, J=8.1 Hz, 8.1 Hz, 1H), 7.34(d, J=8.1 Hz, 1H), 7.72 (d, J=8.1 Hz, 1H), 7.99 (s, 1H), 8.38 (d, J=3.9Hz, 1H), 9.67 (s, 1H).

Example 50 Preparation ofN-(3-Methylcarbamoylphenyl)-3-(4-methoxyphenyl)propionamide (CompoundNo. 248 in Table 1)

Melting point: 151-152° C.; IR (KBr, cm⁻¹): 3289, 1669, 1634, 1613,1557, 1514; NMR (DMSO-d₆, δ): 2.57 (t J=7.5 Hz, 2H), 2.77 (d, J=4.2 Hz,3H), 2.85 (t, J=7.5 Hz, 2H), 3.71 (s, 3H), 6.84 (d, J=8.1 Hz, 2H), 7.16(d, J=8.1 Hz, 2H), 7.35 (dd, J=7.8 Hz, 7.8 Hz, 1H), 7.45 (d, J=7.8 Hz,1H), 7.74 (d. J=7.5 Hz, 1H), 8.01 (s, 1H), 8.34 (d, J=4.2 Hz, 1H), 10.00(s, 1H).

Example 51 Preparation ofN′-Methyl-3-(4-methylbenzyloxycarbonylamino)benzamide (Compound No. 51in Table 2)

4-Methylbenzylalcohol (307 mg) and di(N-succinimidyl)carbonate (966mg)were dissolved in methylene chloride (20 ml), and triethylamine (0.70ml) was added to the solution. After stirring for 4 hours at roomtemperature, water was added and an aqueous layer was extracted withmethylne chloride. The extracted aqueous layer was successively washedwith an aqueous saturated sodium chloride solution, an aqueous saturatedsodium bicarbonate solution, an aqueous saturated sodium chloridesolution, 2N hydrcroric acid, and an aqueous saturated sodium chloridesolution, and dried over magnesia sulfite. After removing magnesiumsulfate by titration, the filtrate was concentrated to obtainN-(4-methylbenzyloxycarbonyloxy)succinate imide (664 mg) as anintermediate.

N-(4-methylbenzyloxycarbonyloxy)succinate imide (610 mg of theabove-obtained product) was dissolved in dimethylformanmide (2 ml), and3-aminobenzoylmethylamide (313 mg) and triethylamine (0.32 ml) wereadded thereto. After stirring overnight at room temperature, theobtained insoluble material was added to water (15 ml) while theinsoluble products are being filtered. The crystals obtained fromfiltrate was filtered and washed with water to obtain crude crystals.The crude crystals were dried and added to ethyl acetate (8 ml), and washeated under reflux for 10 minutes. The mixture was cooled to roomtemperature, and the crystals were collected by filtration and washedwith ethyl acetate to obtain the desired compound (167 mg, yield 27%).

Melting Point: 167-168° C.; IR(KBr, cm⁻¹): 3322, 1738, 1622, 1557;NMR(DMSO-d₆, δ): 2.28(s, 3H), 2.74(d, J=4.6 Hz, 3H), 5.09(s, 2H),7.17(d, J=7.9 Hz, 2H), 7.23-7.42(m, 4H), 7.54(d, J=6.5 Hz, 1H), 7.91(s,1H), 8.31(d, J=4.61 Hz, 1H), 9.82(s, 1H).

In similar manners to the method of Example 51, compounds of Example52-68 and Example 72 were prepared. Their physicochemical propertes areset out below.

Example 52 Preparation ofN′-Methyl-3-(2-fluorobenzyloxycarbonylamino)benzamide (Compound No. 17in Table 2)

Melting Point: 189-190° C.; IR(KBr, cm⁻¹): 3341, 3291, 1730, 1622, 1557;NMR(DMSO-d₆, δ): 2.76(d, J=4.2 Hz, 3H), 5.22(s, 2H), 7.20-7.45(m, 5H),7.50-7.60(m, 2H), 7.94(s, 1H), 8.36(d, J=4.2 Hz, 1H), 9.53(s, 1H).

Example 53 Preparation ofN′-Methyl-3-(4-fluorobenzyloxycarbonylamino)benzamide (Compound No. 21in Table 2)

Melting Point: 153° C.; IR(KBr, cm⁻¹): 3304, 1732, 1626, 1613, 1559;NMR(DMSO-d₆, δ): 2.76(d, J=3.4 Hz, 3H), 5.15(s, 2H), 7.23(dd, J=8.6 Hz,8.6 Hz, 2H), 7.35(dd, J=7.7 Hz, 7.4 Hz, 1H), 7.42(d, J=7.4 Hz, 1H),7.49(dd, J=8.6 Hz, 8.6 Hz, 2H), 7.57(d, J=7.7 Hz 1H), 7.94(s, 1H),8.36(d, J=3.4 Hz, 1H), 9.90(s, 1H).

Example 54 Preparation ofN′-Methyl-3-(2-chlorobenzyloxycarbonylamino)benzamide (Compound No. 23in Table 2)

Melting Point: 168° C.; IR(KBr, cm⁻¹): 3329, 3289, 1728, 1622, 1559;NMR(DMSO-d₆, δ): 2.74(d, J=4.4 Hz, 3H), 5.23(s, 2H), 7.27-7.43(m, 4H),7.43-7.60(m, 3H), 7.93(s, 1H), 8.30(d, J=4.4 Hz, 1H), 9.94(s, 1H).

Example 56 Preparation ofN′-Methyl-3-(4-chlorobenzyloxycarbonylamino)benzamide (Compound No. 27in Table 2)

Melting Point: 155-156° C.; IR(KBr, cm⁻¹): 3351, 3299, 1734, 1624, 1557;NMR(DMSO-d₆, δ): 2.74(d, J=4.5 Hz, 3H), 5.14(s, 2H), 7.25-7.43(m, 6H),7.55(d, J=8.3 Hz, 1H), 7.91(s, 1H), 8.32(d, J=4.5 Hz, 1H), 9.88(s, 1H).

Example 56 Preparation ofN′-Methyl-3-(2,3-dichlorobenzyloxycarbonylamino)benzamide (Compound No.29 in Table 2)

Melting Point: 167-168° C.; IR(KBr, cm⁻¹): 3401, 3258, 1744, 1711, 1649,1561; NMR(DMSO-d₆, δ): 2.74(d, J=4.4 Hz, 3H), 5.26(s, 2H), 7.25-7.43(m,3H), 7.50-7.60(m, 2H), 7.64(d, J8.0 Hz, 1H), 7.93(s, 1H), 8.32(d, J=4.4Hz, 1H), 9.97(s, 1H).

Example 57 Preparation ofN′-Methyl-3-(2,6-dichlorobenzyloxycarbonylamino)benzamide (Compound No.35 in Table 2)

Melting Point: 219-220° C.; IR(KBr, cm⁻¹): 3380, 3241, 1717, 1651, 1562;NMR(DMSO-d₆, δ): 2.74(d, J=4.3 Hz, 3H), 5.35(s, 2H), 7.25-7.60(m, 6H),7.92(s, 1H), 8.35(d, J=4.3 Hz, 1H), 9.92(s, 1H).

Example 58 Preparation ofN′-Methyl-3-(2-bromobenzyloxycarbonylamino)bezamide (Compound No. 41 inTable 2)

Melting Point: 163-164° C.; IR(KBr, cm⁻¹): 3324, 1728, 1622, 1559;NMR(DMSO-d₆, δ): 2.73(d, J=4.0 Hz, 3H), 5.19(s, 2H), 7.24-7.75(m, 7H),7.93(s, 1H), 8.35(d, J=4.0 Hz, 1H), 9.98(s, 1H).

Example 59 Preparation ofN′-Methyl-3-(2-methylbenzyloxycarbonylamio)benzamide (Compound No. 47 inTable 2)

Melting Point: 163° C.; IR(KBr, cm⁻¹): 3358, 3312, 1734, 1622, 1557;NMR(DMSO-d₆, δ): 2.35(s, 3H), 2.76(d, J=4.4 Hz, 3H), 5.17(s, 2H),7.18-7.35(m, 3H), 7.35-7.45(m, 3H), 7.57(d, J=7.7 Hz, 1H), 7.94(s, 1H),8.37(d, J=4.4 Hz, 1H), 9.89(s, 1H).

Example 60 Preparation ofN′-Methyl-3-(3-methylbenzyloxycarbonylamino)benzamide (Compound No. 49in Table 2)

Melting Point: 155° C.; IR(KBr, cm⁻¹): 3343, 3279, 1736, 1624, 1559;NMR(DMSO-d₆, δ): 2.32(s, 3H), 2.76(d, J=4.2 Hz, 3H), 5.12(s, 2H),7.10-7.45(m, 6H), 7.57(d, J=8.0 Hz, 1H), 7.94(s, 1H), 8.36(d, J=4.2 Hz,1H), 9.89(s, 1H).

Example 61 Preparation ofN′-Methyl-3-(4-isopxopylbenzyloxycarbonylamino)benzamide (Compound No.57 in Table 2)

Melting Point: 189-190° C.; IR(KBr, cm⁻¹): 3380, 3235, 1709, 1647, 1561;NMR(DMSO-d₆, δ): 1.19(d, J=6.8 Hz, 6H), 2.76(d, J=3.9 Hz, 3H), 2.88(m,1H), 5.12(s, 2H), 7.20-7.40(m, 6H), 7.57(d, J=7.7 Hz, 1H), 7.93(s, 1H),8.35(d, J=3.9 Hz, 1H), 9.87(s, 1H).

Example 62 Preparation ofN′-Methyl-3-(2-methoxybenzytoxycarbonylamino)benzamide (Compound No. 61in Table 2)

Melting Point: 173° C.; IR(KBr, cm⁻¹): 3341, 3266, 1726, 1624, 1561;NMR(DMSO-d₆, δ): 2.76(d, J=4.0 Hz, 3H), 3.82(s, 3H), 5.14(s, 2H),6.99(dd, J=7.4 Hz, 1H), 7.04(d, J=8.2 Hz, 1H), 7.28-7.42(m, 4H), 7.56(d,J=8.2 Hz, 1H), 7.94(s, 1H), 8.36(d, J=4.0 Hz, 1H), 9.89(s, 1H).

Example 63 Preparation ofN′-Methyl-3-(4-methoxybenzyloxycarbonylamino)benzamide (Compound No. 65in Table 2)

Melting Point: 158-159° C.; IR(KBr, cm⁻¹): 3331, 3295, 1730, 1613, 1555;NMR(DMSO-d₆, δ): 2.74(d, J=4.3 Hz, 3H), 3.73(s, 3H), 5.06(s, 2H),6.92(d, J=8.2 Hz, 2H, 7.20-7.40(m, 4H), 7.54(d, J=7.7 Hz, 1M), 7.90(s,1H), 8.30(d, J=4.3 Hz, 1H), 9.78(s, 1H).

Example 64 Preparation ofN′-Methyl-3-(4-chloro2-nitrobenzyloxycarbonylamino)benzamide (CompoundNo. 77 in Table 2)

Melting Point: 193° C.; IR(KBr, cm⁻¹): 3366, 3248, 1717, 1624, 1662,1537; NMR(DMSO-d₆, δ): 2.76(d, J=3.3 Hz, 3H), 5.48(s, 2H), 7.36(dd,J=7.8 Hz, 7.8 Hz, 1H), 7.44 (d, J=7.8 Hz, 1H), 7.58(d, J=7.8 Hz, 1H),7.77(d, J=8.1 Hz, 1H), 7.90-7.98(m, 2H), 8.23(s, 1H), 8.35(d, J=3.3 Hz,1H), 10.04(s, 1H).

Example 65 Preparation ofN′-Methyl-3-(1-naphthylmethoxycarbonylamino)benzamide (Compound No. 81in Table 2)

Melting Point: 228-229° C.; IR(KBr, cm⁻¹): 3353, 3285, 1730, 1626, 1555;NMR(DMSO-d₆, δ): 2.76(d, J=4.4 Hz, 3H), 5.64(s, 2H), 7.30-7.45(m, 2H),7.50-7.70(m, 5H), 7.90-8.03(m, 3H), 8.12(d, J=7.6 Hz, 1H), 8.38(d, J=4.4Hz, 1H), 9.87(s, 1H).

Example 66 Preparation ofN′-Methyl-3-(2-naphthylmethoxycarbonylamino)benzamide (Compound No. 89in Table 2)

Melting Point: 157-158° C.; IR(KBr, cm⁻¹): 3314, 1699, 1642, 1589, 1539;NMR(DMSO-₆, δ): 2.76(d, J=4.8 Hz, 3H), 5.32(s, 2H), 7.23-7.42(m, 2H),7.42-7.60(m,4H), 7.82-7.98(m, 5H), 8.32(d, J=4.8 Hz, 1H), 9.90(s, 1H).

Example 67 Preparation ofN′-Methyl-3-(5-fluorenylmethoxycarbonylamio)benzamide (Compound No. 99in Table 2)

Melting Point: 217° C.; IR(KBr, cm⁻¹): 3349, 3289, 1730, 1624, 1586,1557; NMR(DMSO-d₆, δ): 2.76(d, J=4.2Hz, 3H), 4,32(t, J=6.6 Hz, 1H),4.48(d, J=6.6 Hz, 2H), 7.25-7.50(m, 6H), 7.59(m, 1H), 7.76(d, J=7.2 Hz,2H, 7.92(d, J=7.2 Hz, 2H), 7.93(s, 1H), 8.37(d, J=4.2 Hz, 1H), 9.87(s,1H).

Example 68 Preparation ofN′-Methyl-3-(phenoxycarbonylamino)benzamide(Compound No. 181 in Table 2)

Melting Point: 193° C.; IR(KBr, cm⁻¹): 3401, 3268, 1763, 1624, 1555;NMR(DMSO-d₆, δ): 2.77(d, J=3.6 Hz, 3H), 7.20-7.35(m, 3H), 7.35-7.45(m,4H), 7.49(d, J=7.8 Hz, 1H), 7.63(s, 1H), 7.99(s, 1H), 10.38(s, 1H).

Example 69 Preparation of1-(3-Methylcarbamoylphenyl)-3-phenylurea(Compound No. 182 in Table 2)

Phenylisocyanate (209 mg) and 3-aminobenzoylmethylamide (239 mg) weredissolved in dimethylformamide (2 ml). After starring for 6 hours atroom temperature, dilute hydrochloric acid (15 ml) was added. Theobtained crystals were filtered and washed with water to obtain crudecrystals. The crude crystals were dried under reduced pressure and addedto ethyl acetate (8 ml), and the mixture was heated under reflux for 10minutes. The mixture was cooled to room temperature, and the crystalswere collected by filtration and washed with ethyl acetate to obtain thedesired compound (386 mg, yield 90%).

Melting Point: 209-210° C.; IR(KBr, cm⁻¹): 3328, 3279, 1699, 1626, 1557;NMR(DMSO-d₆, δ): 2.75(d, J=4.1 Hz, 3H), 6.95(dd, J-7.3 Hz, 7.3 Hz, 1H),7.20-7.45(m, 6H), 7.57(d, J=7.7 Hz, 1H), 7.86(s, 1H), 8.37(d, J=4.1 Hz,1H), 8.67(s, 1H), 8.79(s, 1H).

In similar manners to the method of Example 69, compounds of Example 70and Example 71 were prepared. Their physicochemical properties are setout below.

Example 70 Preparation of3-Benzyl-1-(3-methylcarbamoylphenyl)urea(Compound No. 5 in Table 2)

Melting Point: 189-190° C.; IR(KBr, cm⁻¹): 3366, 3333, 1640, 1559;NMR(DMSO-d₆, δ): 2.73(d, J=4.4 Hz, 3H), 4.28(d, J=5.9 Hz, 2H), 6.62(t,J=5.9 Hz, 1H), 7.15-7.40(m, 7H), 7.54(d, J=7.3 Hz, 1H), 7.79(s, 1H),8.28(d, J=4.4 Hz, 1H), 8.66(s, 1H).

Example 71 Preparation of3-Benzyl-1-(3-methylcarbamoylphenyl)thiourca(Compound No. 6 in Table 2)

Melting Point: 199° C.; IR(KBr, cm⁻¹): 3343, 3246, 3069, 1630, 1584,1528; NMR(DMSO-d₆, δ): 2.76(d, J=4.5 Hz, 3H), 4.72(d, J=5.4 Hz, 2H),7.20-7.40(m, 6H), 7.45-7.60(m, 2H), 7.81(s, 1H), 8.20(s, 1H), 8.36(d,J=4.5 Hz, 1H), 9.65(s, 1H).

Example 72 Preparation of N′-Methyl-3-(2-(2methyl-5-nitro-1-imidazolyl)ethoxycarbonylamino)benzamide (Compound No. 233 in Table 2)

Melting Point: 207° C.; IR(KBr, cm⁻¹): 3362, 1734, 1636, 1591, 1533;NMR(DMSO-d₆, δ): 2.48(s, 3H), 2.76(d, J=4.2 Hz, 3H), 4.47(t, J=4.8 Hz,2H), 4.61(t, J=4.8 Hz, 2H), 7.34(dd, J=7.7 Hz, 7.5 Hz, 1H), 7.43(d,J=7.5 Hz, 1H), 7.55(d, J=7.7 Hz, 1H), 7.85(s, 1H), 8.05(s, 1H), 8.34(d,J=4.4 Hz, 1H), 9.76(s, 1H)

Test Example 1 Measurement of Anti-Helicobacter Pylori Activity

Brain heart infusion culture medium containing 10% fetal bovine serum(Difco) (5 ml) was taken in a test tube, and then the medium wasinoculated with Helicobacter pylori strain 31A isolated from human(obtained from the Metropolitan Health Institute, MicroorganismDepartment, First Laboratory of Bacteria). Cultivation was carried outunder slightly aerobic condition (5% oxygen, 10% carbon dioxide, 85%nitrogen) at 37° C. for 48 hours with shaking.

The culture was then inoculated to brain heart infusion mediumcontaining 10% fetal bovine serum at a ratio of 5%, and added with atest compound dissolved in 10% dimethyl sulfoxide. Cultivation wascarried out under slightly aerobic condition at 37° C. for 48 hours withshaking, and then growth of Helicobacter pylori was examined.Antibacterial activity was recorded as the lowest concentration thatexhibited growth inhibition (minimum inhibitory concentration: MIC). Theresults are shown in Tables 3 and 4. From the results shown in Tables 3and 4, it can be understood that the compounds of the present inventionhave potent inhibitory activity against Helicobacter pylori.

TABLE 3 Example No. (Compound No. in Table 1) MIC (μg/ml)  1 (No. 17)0.39  3 (No. 7) 1.56  8 (No. 18) 0.78 10 (No. 22) 0.39 16 (No. 33) 0.7817 (No. 42) 0.39 18 (No. 43) 0.39 19 (No. 59) 0.78 20 (No. 60) 0.78 22(No. 62) 1.56 23 (No. 63) 0.78 24 (No. 68) 0.78 30 (No. 113) 0.10 31(No. 114) 0.05 32 (No. 140) 0.78 33 (No. 146) 0.10 34 (No. 148) 0.20 36(No. 159) 0.78 38 (No. 177) 0.78 41 (No. 191) 0.10 42 (No. 192) 0.39 43(No. 204) 0.39 44 (No. 216) 0.78 45 (No. 219) 0.78 49 (No. 246) 0.78

TABLE 4 Example No. (Compound No. in Table 2) MIC (μg/ml) 51 (No. 51)0.10 52 (No. 17) 0.78 53 (No. 21) 0.78 54 (No. 23) 0.39 55 (No. 27) 0.2056 (No. 29) 0.20 57 (No. 35) 0.20 58 (No. 41) 0.39 59 (No. 47) 0.39 60(No. 49) 0.39 61 (No. 57) 0.78 62 (No. 61) 0.78 63 (No. 65) 0.78 65 (No.81) 0.05 66 (No. 89) 0.10 70 (No. 5) 1.56

Test Example 2 Measurement of Anti-Campylobacter Jejuni Activity

According to a aimiar method to that of Test Example 1, inhibitoryactivity of the compound of the present invention against Campylobacterjejune was determined. As a result, MIC of the compound of Example 31was 0.008 μg/ml. From the result, it can be understood that the compoundof the present invention has potent inhibitory activity againstCampylobacter jejumni.

Test Example 3 Acute Toxicity Test

The compound of the present invention, suspended in 0.5% CMC-Na aqueoussolution, was forcibly administered orally to SD male and female rats,and symptoms of the rats were observed for seven days. As a result, eachof LD₅₀ values of the compounds of Examples 30 and 31 was not lower than2,000 mg/kg.

Formulation Examples

(1) Tablet

The following ingredients were mixed according to a conventional method,and compressed to obtain a tablet by using a conventional apparatus.

Compound of Example 31 100 mg Crystalline cellulose 180 mg Corn Starch300 mg Lactose 600 mg Magnesium stearate  15 mg

(2) Soft capsule

The following ingredients were mixed according to a conventional method,and filled in a soft capsule.

Compound of Example 41 100 mg Olive oil 900 mg Lecithin  60 mg

Industrial Applicability

The amide derivatives of the present invention have potent antibacterialactivity against Helicobacter pylori, and therefore, they are useful asan active ingredient of medicaments.

What is claimed is:
 1. A compound represented by the following generalformula (I):

wherein X represents R¹(R²)(R³)C— where R¹ represents a C₃-C₈ cycloalkylgroup, an optionally substituted C₆-C₁₄ aryl group, an optionallysubstituted C₆-C₁₄ aryloxy group, or an optionally substituted C₇-C₁₅arylmethyl group; R² and R³ independently represent hydrogen atom or aC₁-C₅ alkyl group, or R² and R³ may combine to represent a C₂-C₇alkylene group; or X represents R⁷—A— wherein R⁷ represents (i) a C1-C10alkyl group which may optionally be substituted with an optionallysubstituted C6-C14 aryl group, or an optionally substituted fluorenylgroup, or (ii) an optionally substituted C6-C14 aryl group, and Arepresents an oxygen atom or —N—R⁸ where R⁸ represents hydrogen atom ora C1-C5 alkyl group, Y represents an oxygen atom or a sulfur atom, R⁴represents hydrogen atom or a C₁-C₅ alkyl group; R⁵ represents hydrogenatom; and R⁶ represents a C₁-C₂ alkyl group which may optionally besubstituted with a hydroxyl group, a hydroxyl group or a C₁-C₂ alkoxygroup, provided that the compounds wherein R⁷ is a benzyl group, A and Yare an oxygen atom, R⁴ and R⁵ are hydrogen atom, and R⁶ is a propylgroup are excluded, or a salt thereof or a solvate thereof or a hydratethereof.
 2. The compound according to claim 1 or a salt thereof, or asolvate thereof or a hydrate thereof, wherein R⁴ is hydrogen atom. 3.The compound according to claim 1 or a salt thereof, or a solvatethereof or a hydrate thereof, wherein R⁶ is a C₁-C₂ alkyl group.
 4. Thecompound according to claim 3 or a salt thereof, or a solvate thereof ora hydrate thereof, wherein R⁶ is methyl group.
 5. The compound accordingto claim 1 or a salt thereof, or a solvate thereof or a hydrate thereof,wherein Y is an oxygen atom.
 6. The compound according to claim 5 or asalt thereof, or a solvate thereof or a hydrate thereof, wherein X isR¹(R²)(R³)C—.
 7. The compound according to claim 6 or a salt thereof, ora solvate thereof or a hydrate thereof, wherein R² and R³ are hydrogenatoms.
 8. The compound according to claim 6 or a salt thereof, or asolvate thereof or a hydrate thereof, wherein R¹ is a C₆-C₁₄ aryl groupwhich may optionally be substituted.
 9. The compound according to claim6 or a salt thereof, or a solvate thereof or a hydrate thereof, whereinR¹ is a C₆-C₁₄ aryloxy group which may optionally be substituted. 10.The compound according to claim 6 or a salt thereof, or a solvatethereof or a hydrate thereof, wherein R¹ is a C₇-C₁₆ arylmethyl groupwhich may optionally be substituted.
 11. The compound according to claim1 or a salt thereof, or a rolvate thereof or a hydrate thereof, whereinX is R⁷—A—.
 12. The compound according to claim 11 or a salt thereof, ora solvate thereof or a hydrate thereof, wherein A is an oxygen atom or—N—H.
 13. The compound according to claim 11 or a salt thereof, or asolvate thereof or a hydrate thereof, wherein R⁷ is a C1to C10 alkylgroup which may optionally be substituted with an opionally substitutedC6-C14 aryl group.
 14. The compound according to claim 13 or a saltthereof, or a solvate thereof or a hydrate thereof wherein R⁷ is a C1 toC5 alkyl group which may optionally be substituted with an optionallysubstituted C6-C14 aryl group.
 15. The compound according to claim 14 ora salt thereof, or a solvate thereof or a hydrate thereof, wherein R⁷ isa methyl group which may optionally be substituted with an optionallysubstituted C6-C14 aryl group.
 16. The compound according to claim 15 ora salt thereof, or a solvate thereof or a hydrate thereof, wherein R⁷ isa methyl group which is substituted with an optionally substitutedC6-C14 aryl group.
 17. A compound selected from the group consirting of:N′-methyl-3-(2-chlorobenzyloxycarbonylamino)benzamide;N′-methyl-3-(4-chlorobenzyloxycarbonylamino)benzamide; N′-methyl-3-(2,3-dichlorobenzyloxycarbonylamino)benzamide; N′-methyl-3-(2,6-dichlorobenzyloxycarbonylamino)benzamide;N′-methyl-3-(2-bromobenzyloxycarbonylamino)benzamide;N′-methyl-3-(2-methylbenzyloxycarbonylamino)benzamide;N′-methyl-3-(3-methylbenzyloxycarbonylamino)benzamide;N′-methyl-3-(4-methylbenzyloxycarbonylamino)benzamide;N′-methyl-3-(1-naphthylmethoxycarbonylamino)benzamide; andN′-methyl-3-(2-naphthylmethoxycarbonylamino)benzamide; or apharmaceutically acceptable salt thereof, or a solvate thereof or ahydrate thereof.
 18. N-(3-methylcarbamoylphenyl)-1-naphthylacetamide ora pharmaceutically acceptable salt thereof, or a solvate thereof or ahydrate thereof.
 19. N-(3-methylcarbamoylphenyl)-2-naphthylacetanide ora pharmaceutically acceptable salt thereof, or a solvate thereof or ahydrate thereof.
 20. N-(3-methylcarbamoylphenyl)-1-naphthyloxyacetamideor a pharmaceutically acceptable salt thereof, or a solvate thereof or ahydrate thereof.
 21. A medicament comprising as an active ingredient asubstance selected from the group consisting of a compound according toclaim 1 and a salt thereof, and a solvate thereof and a hydrate thereof.22. The medicament according to claim 21 which is in the form of apharmaceutical composition comprising said substance as an activeingredient and one or more pharmaceutical additives.
 23. The medicamentaccording to claim 21 which has antibacterial activity.
 24. Themedicament according to claim 23 which has antibacterial activityagainst a microorganism belonging to the genus Helicobacter and/orCampylobacter.
 25. The medicament according to claim 24 which hasanti-Helicobacter pylori activity and/or anti-Campylobacter jejuniactivity.
 26. A process for at least one of preventing and treating adigestive disease, comprising administering the medicament accordingclaim
 21. 27. The process of claim 26 wherein the digestive disease isone of gastritis, gastric ulcer, gastric cancer, gastric malignantlymphoma, MALT lymphoma, duodenal ulcer, duodenal carcinoma, andenteritis.
 28. A process for preventing recurrence of a digestivedisease, comprising administering the medicament according to claim 21.29. The process of claim 28 wherein the digestive disease is one ofgastric ulcer and duodenal ulcer.